Variant rs11568653 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005845.5(ABCC4):c.3211G>A(p.Val1071Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000325 in 1,601,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 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: 𝑓 0.0017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ABCC4
NM_005845.5 missense, splice_region

Scores

Splicing: ADA: 0.9175

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0134314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5 linkuse as main transcript	c.3211G>A	p.Val1071Ile	missense_variant, splice_region_variant	26/31	ENST00000645237.2	NP_005836.2	O15439-1A8K2Q2
ABCC4	NM_001301829.2 linkuse as main transcript	c.3070G>A	p.Val1024Ile	missense_variant, splice_region_variant	25/30		NP_001288758.1	O15439-2A8K2Q2
ABCC4	XM_047430034.1 linkuse as main transcript	c.3082G>A	p.Val1028Ile	missense_variant, splice_region_variant	26/31		XP_047285990.1
ABCC4	XM_047430035.1 linkuse as main transcript	c.2662G>A	p.Val888Ile	missense_variant, splice_region_variant	23/28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.3211G>A	p.Val1071Ile	missense_variant, splice_region_variant	26/31		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

255

AN:

147008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00619

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000349

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000226

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00101

GnomAD3 exomes

AF:

0.000536

AC:

126

AN:

234958

Hom.:

AF XY:

0.000370

AC XY:

AN XY:

127182

show subpopulations

Gnomad AFR exome

AF:

0.00690

Gnomad AMR exome

AF:

0.000548

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:

0.000537

GnomAD4 exome

AF:

0.000182

AC:

264

AN:

1454254

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

722964

show subpopulations

Gnomad4 AFR exome

AF:

0.00644

Gnomad4 AMR exome

AF:

0.000440

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:

0.00000541

Gnomad4 OTH exome

AF:

0.000416

GnomAD4 genome

AF:

0.00174

AC:

256

AN:

147128

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

119

AN XY:

71372

show subpopulations

Gnomad4 AFR

AF:

0.00620

Gnomad4 AMR

AF:

0.000348

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000226

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000298

Gnomad4 OTH

AF:

0.000998

Alfa

AF:

0.000308

Hom.:

Bravo

AF:

0.00215

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000544

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

.;T;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.53

N;N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.42

.;N;.

REVEL

Uncertain

0.37

Sift

Benign

0.30

.;T;.

Sift4G

Benign

0.39

.;T;.

Polyphen

0.058

B;B;B

Vest4

0.13

MVP

0.57

MPC

0.20

ClinPred

0.0084

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.080

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Benign

0.58

SpliceAI score (max)

0.10

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