11-119150202-G-T

Variant names:

• chr11-119150202-G-T
• rs193920956
• NM_022169.5:c.237G>T

Variant summary

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

The NM_022169.5(ABCG4):​c.237G>T​(p.Arg79Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCG4 NM_022169.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003794
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.04

Genes affected

ABCG4 (HGNC:13884): (ATP binding cassette subfamily G member 4) The protein encoded by this gene is a member of the ATP-binding cassette (ABC) transporter superfamily. 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). The encoded protein is a member of the White subfamily and plays an important role in cellular cholesterol homeostasis. This protein functions as either a homodimer or as a heterodimer with another ABC subfamily protein such as ABCG1. [provided by RefSeq, Jan 2017]

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=0.34245098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG4	NM_022169.5	c.237G>T	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 15	ENST00000619701.5	NP_071452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG4	ENST00000619701.5	c.237G>T	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 15	1	NM_022169.5	ENSP00000481728.1
ABCG4	ENST00000622721.1	c.237G>T	p.Arg79Ser	missense_variant, splice_region_variant	Exon 1 of 14	1		ENSP00000484289.1
ABCG4	ENST00000615496.4	c.237G>T	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 15	2		ENSP00000479253.1
ABCG4	ENST00000524604.5	c.237G>T	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 4	3		ENSP00000431915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	.;T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.46	N;.;N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.0	.;D;.;.
REVEL	Benign	0.19
Sift	Benign	0.11	.;T;.;.
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.65	P;.;P;P
Vest4		0.63
MutPred		0.48		Loss of MoRF binding (P = 0.0335);Loss of MoRF binding (P = 0.0335);Loss of MoRF binding (P = 0.0335);Loss of MoRF binding (P = 0.0335);
MVP		0.62
ClinPred		0.90	D
GERP RS		2.4
Varity_R		0.24
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00038
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.12		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: rs193920956; hg19: chr11-119020912; COSMIC: COSV56646047; COSMIC: COSV56646047;