Genetic Variant ABCC4:p.Arg317Arg (chr13-95206742-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005845.5(ABCC4):c.951A>G(p.Arg317Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,613,596 control chromosomes in the GnomAD database, including 328,042 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.

Frequency

Genomes: 𝑓 0.56 ( 24595 hom., cov: 32)

Exomes 𝑓: 0.64 ( 303447 hom. )

Consequence

ABCC4
NM_005845.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.229 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.951A>G	p.Arg317Arg	synonymous_variant	Exon 8 of 31	ENST00000645237.2	NP_005836.2	O15439-1A8K2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 link	c.951A>G	p.Arg317Arg	synonymous_variant	Exon 8 of 31		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84548

AN:

151956

Hom.:

24601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.557

GnomAD3 exomes

AF:

0.602

AC:

151391

AN:

251296

Hom.:

46633

AF XY:

0.610

AC XY:

82788

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.641

AC:

937152

AN:

1461522

Hom.:

303447

Cov.:

AF XY:

0.642

AC XY:

466701

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.548

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.662

Gnomad4 OTH exome

AF:

0.609

GnomAD4 genome

AF:

0.556

AC:

84561

AN:

152074

Hom.:

24595

Cov.:

AF XY:

0.553

AC XY:

41087

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.552

Alfa

AF:

0.605

Hom.:

22395

Bravo

AF:

0.539

Asia WGS

AF:

0.538

AC:

1871

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.73

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