Variant chr13-95210754-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005845.5(ABCC4):c.559G>T(p.Gly187Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0308 in 1,613,498 control chromosomes in the GnomAD database, including 1,431 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.032 ( 161 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1270 hom. )

Consequence

ABCC4
NM_005845.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) 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 MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ABCC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052810013).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5 linkuse as main transcript	c.559G>T	p.Gly187Trp	missense_variant	5/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.559G>T	p.Gly187Trp	missense_variant	5/31		NM_005845.5	P1	O15439-1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4849

AN:

152130

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0871

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0576

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0490

AC:

12291

AN:

251012

Hom.:

509

AF XY:

0.0474

AC XY:

6431

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00462

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0405

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.0620

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0433

GnomAD4 exome

AF:

0.0307

AC:

44919

AN:

1461250

Hom.:

1270

Cov.:

AF XY:

0.0316

AC XY:

22972

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.0612

Gnomad4 FIN exome

AF:

0.0381

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0311

GnomAD4 genome

AF:

0.0318

AC:

4846

AN:

152248

Hom.:

161

Cov.:

AF XY:

0.0355

AC XY:

2643

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00477

Gnomad4 AMR

AF:

0.0871

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0579

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.0235

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0285

Hom.:

246

Bravo

AF:

0.0356

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0228

AC:

196

ExAC

AF:

0.0447

AC:

5430

Asia WGS

AF:

0.0720

AC:

249

AN:

3478

EpiCase

AF:

0.0263

EpiControl

AF:

0.0277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;D;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

MetaRNN

Benign

0.0053

T;T;T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.6

H;H;H;.;H;.

MutationTaster

Benign

0.0000020

P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.6

.;D;.;D;.;.

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

.;D;.;D;.;.

Sift4G

Uncertain

0.0030

.;D;.;D;D;.

Polyphen

1.0

D;D;D;.;.;.

Vest4

0.18, 0.35, 0.36

MPC

0.85

ClinPred

0.086

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.91

gMVP

0.69

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

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