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Table 4 ClinVar pathogenic/likely pathogenic variants of familial hypercholesterolemia in the Qatar Genome Program study

From: Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank

Gene

dbSNP

cDNA change

Amino-acid change

QGP AC

Max AF in public databases

QGP subcluster

Estimated clinical penetrance

ClinVar

ClinVar Phenotype

ABCG5

rs199689137

c.1336 C>T

p.Arg446*

27

0.0006

QGP_ADM (1), QGP_GAR(24), QGP_PAR(1), QGP_WEP (1)

.

P

Sitosterolemia 1

ABCG8

rs137852991

c.1234 C>T

p.Arg412*

1

6.67E-05

QGP_ADM

.

P

Sitosterolemia 2

ABCG8

rs137852988

c.1720G>A

p.Gly574Arg

6

4.49E-05

QGP_WEP

100% (1/1)*

P/LP

Sitosterolemia 2

APOB

.

c.2817-2 A>C

.

2

0

QGP_ADM

.

LP

Hypobetalipoproteinemia

APOB

.

c.1468 C>T

p.Arg490Trp

2

1.79E-05

QGP_ADM (1), QGP_GAR (1)

.

P

Hypobetalipoproteinemia

LDLR

rs879254809

c.1154T>G

p.Leu385Arg

1

0

QGP_AFR

0% (0/1)

LP

Familial Hypercholesterolemia

LDLR

rs758194385

c.1691 A>G

p.Asn564Ser

1

1.74E-04

QGP_GAR

100% (1/1)

LP

Familial Hypercholesterolemia

LDLR

rs771019366

c.269 A>G

p.Asp90Gly

3

8.24E-06

QGP_WEP(2), QGP_ADM(1)

67% (2/3)

P/LP

Familial Hypercholesterolemia

LDLR

rs1064793799

c.313+3 A>C

.

6

0

QGP_PAR(6)

83% (5/6)

P

Familial Hypercholesterolemia

LIPA

.

c.863 C>T

p.Thr288Ile

1

0

QGP_SAS

.

LP

Lysosomal acid lipase deficiency

  1. QGP_AC: QGP allele count. The maximum AF reported was observed in ExAC and gnomAD exome databases. The numbers in brackets in QGP_subclusters represent the allele count belonging to a specific sub-cluster carrying the variant. General Arabs (QGP_GAR), Peninsular Arabs (QGP_PAR), Arabs of Western Eurasia and Persia (QGP_WEP), South Asians (QGP_SAS), Africans (QGP_AFR) and Admixed (QGP_ADM). Estimated clinical penetrance was calculated based on the total number of definite, probable, and possible FH individuals carrying the variants in the QBB cohort. * Estimated clinical penetrance was calculated for the homozygous individual carrying the ABCG8 recessive variant. Clinvar significance: P – Pathogenic; LP – Likely Pathogenic