2-43840680-T-G

Variant names:

• chr2-43840680-T-G
• rs4148202
• NM_022437.3:c.63+1564T>G

Variant summary

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

The NM_022437.3(ABCG8):​c.63+1564T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,016 control chromosomes in the GnomAD database, including 19,714 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 0.50 (19714 hom., cov: 32)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 8 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: ClinGen, Orphanet, Illumina
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG8	NM_022437.3	MANE Select	c.63+1564T>G		intron	N/A	NP_071882.1
	ABCG8	NM_001357321.2		c.63+1564T>G		intron	N/A	NP_001344250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG8	ENST00000272286.4	TSL:1 MANE Select	c.63+1564T>G		intron	N/A	ENSP00000272286.2
	ABCG8	ENST00000644611.1		c.76-3827T>G		intron	N/A	ENSP00000495423.1
	ABCG8	ENST00000643284.1		n.521-3827T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76033 AN: 151898 Hom.: 19684 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.501 AC: 76104 AN: 152016 Hom.: 19714 Cov.: 32 AF XY: 0.504 AC XY: 37440 AN XY: 74308

African (AFR) AF: 0.568 AC: 23528 AN: 41412

American (AMR) AF: 0.448 AC: 6846 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4362 AN: 5178

South Asian (SAS) AF: 0.629 AC: 3024 AN: 4808

European-Finnish (FIN) AF: 0.470 AC: 4966 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30230 AN: 67982

Other (OTH) AF: 0.494 AC: 1043 AN: 2112

Alfa AF: 0.450 Hom.: 9287

Bravo AF: 0.498

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		0.063
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: rs4148202; hg19: chr2-44067819;