Variant chr2-43846742-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022437.3(ABCG8):c.322+431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 269,698 control chromosomes in the GnomAD database, including 75,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 43928 hom., cov: 31)

Exomes 𝑓: 0.73 ( 31501 hom. )

Consequence

ABCG8
NM_022437.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

Variant links:

Genes affected

ABCG8 (HGNC:13887): (ATP binding cassette subfamily G member 8) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

ABCG8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-43846742-T-C is Benign according to our data. Variant chr2-43846742-T-C is described in ClinVar as [Benign]. Clinvar id is 1164919.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-43846742-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG8	NM_022437.3 link	c.322+431T>C		intron_variant		ENST00000272286.4	NP_071882.1	Q9H221-1
ABCG8	NM_001357321.2 link	c.322+431T>C		intron_variant			NP_001344250.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCG8	ENST00000272286.4 link	c.322+431T>C	intron_variant		1	NM_022437.3	ENSP00000272286.2	Q9H221-1
ABCG8	ENST00000644611.1 link	c.334+431T>C	intron_variant				ENSP00000495423.1	A0A2R8Y6M1
ABCG8	ENST00000643284.1 link	n.1210T>C	non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114824

AN:

152052

Hom.:

43866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.837

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.725

GnomAD4 exome

AF:

0.728

AC:

85614

AN:

117528

Hom.:

31501

Cov.:

AF XY:

0.730

AC XY:

44937

AN XY:

61584

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.792

Gnomad4 ASJ exome

AF:

0.720

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.755

AC:

114941

AN:

152170

Hom.:

43928

Cov.:

AF XY:

0.763

AC XY:

56787

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.838

Gnomad4 AMR

AF:

0.763

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.771

Gnomad4 FIN

AF:

0.791

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.697

Hom.:

56359

Bravo

AF:

0.759

Asia WGS

AF:

0.887

AC:

3083

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over