rs4952688

Positions:

• chr2-43869631-T-A
• chr2-43869631-T-C
• chr2-43869631-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022437.3(ABCG8):​c.965-2345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 151,862 control chromosomes in the GnomAD database, including 50,560 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50560 hom., cov: 31)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• 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	c.965-2345T>A		intron_variant		ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2	c.965-2345T>A		intron_variant			NP_001344250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG8	ENST00000272286.4	c.965-2345T>A		intron_variant		1	NM_022437.3	ENSP00000272286	P1
ABCG8	ENST00000644611.1	c.977-2345T>A		intron_variant				ENSP00000495423

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123155 AN: 151744 Hom.: 50506 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.784

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.792

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123264 AN: 151862 Hom.: 50560 Cov.: 31 AF XY: 0.817 AC XY: 60594 AN XY: 74206

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.794

Alfa AF: 0.763 Hom.: 5235

Bravo AF: 0.817

Asia WGS AF: 0.932 AC: 3237 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.067
DANN	Benign	0.13

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

Other links and lift over

dbSNP: rs4952688; hg19: chr2-44096770;