13-95044286-C-T

Variant names:

• chr13-95044286-C-T
• rs11568695
• NM_005845.5:c.3609G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000645237.2(ABCC4):​c.3609G>A​(p.Ala1203Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00873 in 1,612,258 control chromosomes in the GnomAD database, including 952 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 0.045 (504 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (448 hom.)
• Consequence: ABCC4 ENST00000645237.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 14 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-0.745 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645237.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.3609G>A	p.Ala1203Ala	synonymous	Exon 28 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.3468G>A	p.Ala1156Ala	synonymous	Exon 27 of 30	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3609G>A	p.Ala1203Ala	synonymous	Exon 28 of 31	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3468G>A	p.Ala1156Ala	synonymous	Exon 27 of 30	ENSP00000494751.1
	ABCC4	ENST00000471041.2	TSL:4	n.479G>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6787 AN: 152156 Hom.: 502 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0116 AC: 2887 AN: 249130 AF XY: 0.00851

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00784

Gnomad ASJ exome AF: 0.00708

Gnomad EAS exome AF: 0.000437

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000894

Gnomad OTH exome AF: 0.00745

GnomAD4 exome AF: 0.00498 AC: 7276 AN: 1459984 Hom.: 448 Cov.: 31 AF XY: 0.00438 AC XY: 3181 AN XY: 726230

African (AFR) AF: 0.154 AC: 5148 AN: 33398

American (AMR) AF: 0.00944 AC: 420 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00824 AC: 215 AN: 26082

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39642

South Asian (SAS) AF: 0.000268 AC: 23 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00729 AC: 42 AN: 5758

European-Non Finnish (NFE) AF: 0.000677 AC: 752 AN: 1111210

Other (OTH) AF: 0.0111 AC: 672 AN: 60308

GnomAD4 genome AF: 0.0447 AC: 6805 AN: 152274 Hom.: 504 Cov.: 33 AF XY: 0.0442 AC XY: 3292 AN XY: 74444

African (AFR) AF: 0.152 AC: 6330 AN: 41534

American (AMR) AF: 0.0186 AC: 285 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68036

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0158 Hom.: 695

Bravo AF: 0.0503

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.42
DANN	Benign	0.58
PhyloP100		-0.74
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: rs11568695; hg19: chr13-95696540;