rs1189466

chr13-95074287-A-Gchr13-95074287-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005845.5(ABCC4):c.2844T>C(p.Phe948=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,613,470 control chromosomes in the GnomAD database, including 726,445 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 0.93 (66603 hom., cov: 32)
  • Exomes 𝑓: 0.95 (659842 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.2844T>C	p.Phe948=	synonymous_variant	23/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.2703T>C	p.Phe901=	synonymous_variant	22/30
ABCC4	XM_047430034.1	c.2715T>C	p.Phe905=	synonymous_variant	23/31
ABCC4	XM_047430035.1	c.2295T>C	p.Phe765=	synonymous_variant	20/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.2844T>C	p.Phe948=	synonymous_variant	23/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142204 AN: 152160 Hom.: 66549 Cov.: 32

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.945

GnomAD3 exomes AF: 0.934 AC: 233658 AN: 250290 Hom.: 109349 AF XY: 0.937 AC XY: 126742 AN XY: 135236

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.960

Gnomad EAS exome AF: 0.795

Gnomad SAS exome AF: 0.956

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.939

GnomAD4 exome AF: 0.950 AC: 1387529 AN: 1461192 Hom.: 659842 Cov.: 47 AF XY: 0.950 AC XY: 690404 AN XY: 726842

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 0.960

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.916

Gnomad4 NFE exome AF: 0.959

Gnomad4 OTH exome AF: 0.943

GnomAD4 genome AF: 0.935 AC: 142316 AN: 152278 Hom.: 66603 Cov.: 32 AF XY: 0.933 AC XY: 69442 AN XY: 74452

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.946

Alfa AF: 0.951 Hom.: 148215

Bravo AF: 0.936

Asia WGS AF: 0.874 AC: 3041 AN: 3478

EpiCase AF: 0.949

EpiControl AF: 0.954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.48
Dann	Benign	0.37

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

Other links and lift over

dbSNP: rs1189466; hg19: chr13-95726541;