chr2-43841152-C-T

Position:

• chr2-43841152-C-T

Variant summary

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

The NM_022437.3(ABCG8):​c.63+2036C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,280 control chromosomes in the GnomAD database, including 156 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 0.038 (156 hom., cov: 32)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG8	NM_022437.3	c.63+2036C>T		intron_variant		ENST00000272286.4
ABCG8	NM_001357321.2	c.63+2036C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG8	ENST00000272286.4	c.63+2036C>T		intron_variant		1	NM_022437.3	P1
ABCG8	ENST00000644611.1	c.76-3355C>T		intron_variant
ABCG8	ENST00000643284.1	n.521-3355C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5794 AN: 152162 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0380 AC: 5794 AN: 152280 Hom.: 156 Cov.: 32 AF XY: 0.0381 AC XY: 2838 AN XY: 74450

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.0540

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0450 Hom.: 127

Bravo AF: 0.0328

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10179921; hg19: chr2-44068291;