chr2-43837951-G-C

Position:

• chr2-43837951-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000405322.8(ABCG5):​c.148C>G​(p.Arg50Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R50C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCG5 ENST00000405322.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) 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 as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34661603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG5	NM_022436.3	c.148C>G	p.Arg50Gly	missense_variant	2/13	ENST00000405322.8	NP_071881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG5	ENST00000405322.8	c.148C>G	p.Arg50Gly	missense_variant	2/13	1	NM_022436.3	ENSP00000384513	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.29
Sift	Benign	0.068	T;.
Sift4G	Uncertain	0.0060	D;.
Polyphen		0.59	P;P
Vest4		0.47
MutPred		0.41		Loss of MoRF binding (P = 0.0367);Loss of MoRF binding (P = 0.0367);
MVP		0.83
MPC		0.15
ClinPred		0.59	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.71

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: rs6756629; hg19: chr2-44065090;