dbSNP rs556090631: ABCG4:p.Ala5Gly (chr11-119149979-C-G) – 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.14C>G(p.Ala5Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A5V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ABCG4
NM_022169.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

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=0.09216815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ABCG4	NM_022169.5 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 15	ENST00000619701.5	NP_071452.2
ABCG4	NM_001142505.1 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 15		NP_001135977.1
ABCG4	NM_001348191.2 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 15		NP_001335120.1
ABCG4	NM_001348192.2 link	c.-225C>G		5_prime_UTR_variant	Exon 2 of 16		NP_001335121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCG4	ENST00000619701.5 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 15	1	NM_022169.5	ENSP00000481728.1	Q9H172-1
ABCG4	ENST00000622721.1 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 14	1		ENSP00000484289.1	Q9H172-1
ABCG4	ENST00000615496.4 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 15	2		ENSP00000479253.1	Q9H172-1
ABCG4	ENST00000524604.5 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 4	3		ENSP00000431915.1	E9PJ00

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244178

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132790

show subpopulations

Gnomad AFR exome

AF:

0.0000629

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;T;T

Eigen

Benign

-0.093

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

.;T;.;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.092

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.31

.;N;.;.

REVEL

Benign

0.036

Sift

Uncertain

0.014

.;D;.;.

Sift4G

Benign

0.080

T;D;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.22

MutPred

0.24

Gain of glycosylation at K4 (P = 0.1013);Gain of glycosylation at K4 (P = 0.1013);Gain of glycosylation at K4 (P = 0.1013);Gain of glycosylation at K4 (P = 0.1013);

MVP

0.55

ClinPred

0.24

GERP RS

3.9

Varity_R

0.13

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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