chr2-43850909-C-CAAAAAAA

Variant names:

• chr2-43850909-C-CAAAAAAA
• rs1164206598
• NM_022437.3:c.323-664_323-658dupAAAAAAA

Variant summary

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

The NM_022437.3(ABCG8):​c.323-664_323-658dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000087 in 57,478 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 0.000087 (0 hom., cov: 33)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 0 publications found

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]

ABCG8 Gene-Disease associations (from GenCC):

• sitosterolemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, ClinGen, Orphanet
• sitosterolemia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG8	NM_022437.3	MANE Select	c.323-664_323-658dupAAAAAAA		intron	N/A	NP_071882.1	Q9H221-1
	ABCG8	NM_001357321.2		c.323-664_323-658dupAAAAAAA		intron	N/A	NP_001344250.1	Q9H221-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG8	ENST00000272286.4	TSL:1 MANE Select	c.323-675_323-674insAAAAAAA		intron	N/A	ENSP00000272286.2	Q9H221-1
	ABCG8	ENST00000881895.1		c.323-675_323-674insAAAAAAA		intron	N/A	ENSP00000551954.1
	ABCG8	ENST00000881900.1		c.323-675_323-674insAAAAAAA		intron	N/A	ENSP00000551959.1

Frequencies

GnomAD3 genomes AF: 0.0000870 AC: 5 AN: 57478 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000721

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000870 AC: 5 AN: 57478 Hom.: 0 Cov.: 33 AF XY: 0.000110 AC XY: 3 AN XY: 27378

African (AFR) AF: 0.00 AC: 0 AN: 14946

American (AMR) AF: 0.00 AC: 0 AN: 5356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1616

East Asian (EAS) AF: 0.00 AC: 0 AN: 1942

South Asian (SAS) AF: 0.00 AC: 0 AN: 1880

European-Finnish (FIN) AF: 0.00104 AC: 3 AN: 2882

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

European-Non Finnish (NFE) AF: 0.0000721 AC: 2 AN: 27732

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1164206598; hg19: chr2-44078048;