Variant chr13-95053126-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005845.5(ABCC4):c.3425C>T(p.Thr1142Met) variant causes a missense change. The variant allele was found at a frequency of 0.00646 in 1,613,900 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 54 hom. )

Consequence

ABCC4
NM_005845.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.44

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013533205).

BP6

Variant 13-95053126-G-A is Benign according to our data. Variant chr13-95053126-G-A is described in ClinVar as [Benign]. Clinvar id is 713177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCC4	NM_005845.5 linkuse as main transcript	c.3425C>T	p.Thr1142Met	missense_variant	27/31	ENST00000645237.2
ABCC4	NM_001301829.2 linkuse as main transcript	c.3284C>T	p.Thr1095Met	missense_variant	26/30
ABCC4	XM_047430034.1 linkuse as main transcript	c.3296C>T	p.Thr1099Met	missense_variant	27/31
ABCC4	XM_047430035.1 linkuse as main transcript	c.2876C>T	p.Thr959Met	missense_variant	24/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.3425C>T	p.Thr1142Met	missense_variant	27/31		NM_005845.5	P1	O15439-1

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

791

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00675

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00665

AC:

1672

AN:

251430

Hom.:

AF XY:

0.00743

AC XY:

1009

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.00680

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00659

AC:

9634

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

4971

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00980

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0129

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.00622

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.00519

AC:

790

AN:

152218

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.00675

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00573

Hom.:

Bravo

AF:

0.00359

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00680

AC:

826

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00486

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;D;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;D;D

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

.;D;.

REVEL

Uncertain

0.53

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.11

.;T;.

Polyphen

0.68

P;P;B

Vest4

0.23

MVP

0.92

MPC

0.82

ClinPred

0.047

GERP RS

5.8

Varity_R

0.16

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over