dbSNP rs193920956: ABCG4:p.Arg79Ser (chr11-119150202-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022169.5(ABCG4):c.237G>C(p.Arg79Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABCG4
NM_022169.5 missense, splice_region

Scores

Splicing: ADA: 0.002383

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04

Variant links:

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]

ABCG4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25552016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG4	NM_022169.5 link	c.237G>C	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	UniProt
ABCG4	ENST00000619701.5 link	c.237G>C	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 15	1	NM_022169.5	ENSP00000481728.1	Q9H172-1
ABCG4	ENST00000622721.1 link	c.237G>C	p.Arg79Ser	missense_variant, splice_region_variant	Exon 1 of 14	1		ENSP00000484289.1	Q9H172-1
ABCG4	ENST00000615496.4 link	c.237G>C	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 15	2		ENSP00000479253.1	Q9H172-1
ABCG4	ENST00000524604.5 link	c.237G>C	p.Arg79Ser	missense_variant, splice_region_variant	Exon 2 of 4	3		ENSP00000431915.1	E9PJ00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250064

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460924

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

.;T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.46

N;.;N;N

PrimateAI

Uncertain

0.79

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

0.51

GERP RS

2.4

Varity_R

0.24

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0024

dbscSNV1_RF

Benign

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over