2-43850909-CAAAAAAAAA-CAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_022437.3(ABCG8):​c.323-658delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0064 (1 hom., cov: 33)
  • Failed GnomAD Quality Control
• 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG8	NM_022437.3	c.323-658delA		intron_variant	Intron 3 of 12	ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2	c.323-658delA		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.323-674delA		intron_variant	Intron 3 of 12	1	NM_022437.3	ENSP00000272286.2
ABCG8	ENST00000644611.1	c.335-674delA		intron_variant	Intron 3 of 8			ENSP00000495423.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 366 AN: 57478 Hom.: 1 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00486

Gnomad ASJ AF: 0.00309

Gnomad EAS AF: 0.00977

Gnomad SAS AF: 0.00319

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.0111

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00637 AC: 366 AN: 57470 Hom.: 1 Cov.: 33 AF XY: 0.00679 AC XY: 186 AN XY: 27384

Gnomad4 AFR AF: 0.00434

Gnomad4 AMR AF: 0.00485

Gnomad4 ASJ AF: 0.00309

Gnomad4 EAS AF: 0.00980

Gnomad4 SAS AF: 0.00322

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.00700

Gnomad4 OTH AF: 0.0111

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;