2-43847292-C-T

Variant names:

• chr2-43847292-C-T
• rs4245791
• NM_022437.3:c.322+981C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022437.3(ABCG8):​c.322+981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,122 control chromosomes in the GnomAD database, including 44,996 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44994 hom., cov: 32)
  • Exomes 𝑓: 0.75 (2 hom.)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 83 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

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.322+981C>T		intron	N/A	NP_071882.1	Q9H221-1
	ABCG8	NM_001357321.2		c.322+981C>T		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.322+981C>T		intron	N/A	ENSP00000272286.2	Q9H221-1
	ABCG8	ENST00000881895.1		c.322+981C>T		intron	N/A	ENSP00000551954.1
	ABCG8	ENST00000881900.1		c.322+981C>T		intron	N/A	ENSP00000551959.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116061 AN: 151996 Hom.: 44935 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.750 AC: 6 AN: 8 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.764 AC: 116175 AN: 152114 Hom.: 44994 Cov.: 32 AF XY: 0.771 AC XY: 57346 AN XY: 74362

African (AFR) AF: 0.869 AC: 36059 AN: 41514

American (AMR) AF: 0.768 AC: 11730 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2531 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5144 AN: 5174

South Asian (SAS) AF: 0.769 AC: 3696 AN: 4806

European-Finnish (FIN) AF: 0.792 AC: 8373 AN: 10578

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46305 AN: 67978

Other (OTH) AF: 0.738 AC: 1555 AN: 2108

Alfa AF: 0.713 Hom.: 117616

Bravo AF: 0.769

Asia WGS AF: 0.889 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4245791; hg19: chr2-44074431;