chr2-43850909-C-CA

Variant names:

• chr2-43850909-C-CA
• rs1164206598
• NM_022437.3:c.323-658dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_022437.3(ABCG8):​c.323-658dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 56,930 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (4 hom., cov: 33)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0135 (769/56930) while in subpopulation EAS AF= 0.0379 (73/1924). AF 95% confidence interval is 0.0309. There are 4 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG8	NM_022437.3	c.323-658dupA		intron_variant	Intron 3 of 12	ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2	c.323-658dupA		intron_variant	Intron 3 of 12		NP_001344250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG8	ENST00000272286.4	c.323-675_323-674insA		intron_variant	Intron 3 of 12	1	NM_022437.3	ENSP00000272286.2
ABCG8	ENST00000644611.1	c.335-675_335-674insA		intron_variant	Intron 3 of 8			ENSP00000495423.1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 771 AN: 56938 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.00625

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0122

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0135 AC: 769 AN: 56930 Hom.: 4 Cov.: 33 AF XY: 0.0145 AC XY: 394 AN XY: 27128

Gnomad4 AFR AF: 0.00844

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs1164206598; hg19: chr2-44078048;