chr2-43850909-CAAAAA-C

Variant names:

• chr2-43850909-CAAAAA-C
• rs1164206598
• NM_022437.3:c.323-662_323-658delAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022437.3(ABCG8):​c.323-662_323-658delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 57,518 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000035 (0 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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG8	NM_022437.3	c.323-662_323-658delAAAAA		intron_variant	Intron 3 of 12	ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2	c.323-662_323-658delAAAAA		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.323-674_323-670delAAAAA		intron_variant	Intron 3 of 12	1	NM_022437.3	ENSP00000272286.2
ABCG8	ENST00000644611.1	c.335-674_335-670delAAAAA		intron_variant	Intron 3 of 8			ENSP00000495423.1

Frequencies

GnomAD3 genomes AF: 0.0000348 AC: 2 AN: 57518 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000360

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000348 AC: 2 AN: 57518 Hom.: 0 Cov.: 33 AF XY: 0.0000365 AC XY: 1 AN XY: 27398

African (AFR) AF: 0.00 AC: 0 AN: 14956

American (AMR) AF: 0.000187 AC: 1 AN: 5356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1618

East Asian (EAS) AF: 0.00 AC: 0 AN: 1944

South Asian (SAS) AF: 0.00 AC: 0 AN: 1882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 86

European-Non Finnish (NFE) AF: 0.0000360 AC: 1 AN: 27752

Other (OTH) AF: 0.00 AC: 0 AN: 716

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;