rs1189466

Variant names:

• chr13-95074287-A-G
• rs1189466
• NM_005845.5:c.2844T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-95074287-A-G
• chr13-95074287-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005845.5(ABCC4):​c.2844T>C​(p.Phe948Phe) 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
• Publications: 30 publications found

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 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.2844T>C	p.Phe948Phe	synonymous_variant	Exon 23 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.2703T>C	p.Phe901Phe	synonymous_variant	Exon 22 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.2715T>C	p.Phe905Phe	synonymous_variant	Exon 23 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.2295T>C	p.Phe765Phe	synonymous_variant	Exon 20 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.2844T>C	p.Phe948Phe	synonymous_variant	Exon 23 of 31		NM_005845.5	ENSP00000494609.1

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

GnomAD2 exomes AF: 0.934 AC: 233658 AN: 250290 AF XY: 0.937

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 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

African (AFR) AF: 0.913 AC: 30527 AN: 33450

American (AMR) AF: 0.934 AC: 41684 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 25087 AN: 26126

East Asian (EAS) AF: 0.763 AC: 30263 AN: 39648

South Asian (SAS) AF: 0.955 AC: 82228 AN: 86098

European-Finnish (FIN) AF: 0.916 AC: 48882 AN: 53382

Middle Eastern (MID) AF: 0.951 AC: 5484 AN: 5764

European-Non Finnish (NFE) AF: 0.959 AC: 1066432 AN: 1111742

Other (OTH) AF: 0.943 AC: 56942 AN: 60370

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

African (AFR) AF: 0.916 AC: 38078 AN: 41554

American (AMR) AF: 0.941 AC: 14384 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3344 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4098 AN: 5170

South Asian (SAS) AF: 0.945 AC: 4557 AN: 4822

European-Finnish (FIN) AF: 0.917 AC: 9733 AN: 10612

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64987 AN: 68036

Other (OTH) AF: 0.946 AC: 2001 AN: 2116

Alfa AF: 0.949 Hom.: 213913

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
PhyloP100		-0.18
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1189466; hg19: chr13-95726541; COSMIC: COSV108230654; COSMIC: COSV108230654;