2-43845437-G-T

Position:

• chr2-43845437-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_022437.3(ABCG8):​c.166-718G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,078 control chromosomes in the GnomAD database, including 43,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.76 (43918 hom., cov: 31)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-43845437-G-T is Benign according to our data. Variant chr2-43845437-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG8	NM_022437.3	c.166-718G>T		intron_variant		ENST00000272286.4
ABCG8	NM_001357321.2	c.166-718G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG8	ENST00000272286.4	c.166-718G>T		intron_variant		1	NM_022437.3	P1
ABCG8	ENST00000644611.1	c.178-718G>T		intron_variant
ABCG8	ENST00000643284.1	n.623-718G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114736 AN: 151960 Hom.: 43859 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.755 AC: 114850 AN: 152078 Hom.: 43918 Cov.: 31 AF XY: 0.763 AC XY: 56715 AN XY: 74344

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.727

Alfa AF: 0.694 Hom.: 82643

Bravo AF: 0.760

Asia WGS AF: 0.885 AC: 3078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.020
DANN	Benign	0.37

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: rs4299376; hg19: chr2-44072576;