13-95234600-T-C

Variant names:

• chr13-95234600-T-C
• rs11568637
• NM_005845.5:c.531+10A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.531+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,607,928 control chromosomes in the GnomAD database, including 267 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 0.016 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (210 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.531+10A>G		intron_variant	Intron 4 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.531+10A>G		intron_variant	Intron 4 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2402 AN: 152130 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00398

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0145 AC: 3623 AN: 250690 AF XY: 0.0139

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.0966

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00375

Gnomad OTH exome AF: 0.00753

GnomAD4 exome AF: 0.00743 AC: 10822 AN: 1455680 Hom.: 210 Cov.: 30 AF XY: 0.00776 AC XY: 5621 AN XY: 724682

African (AFR) AF: 0.0343 AC: 1143 AN: 33314

American (AMR) AF: 0.00313 AC: 140 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26092

East Asian (EAS) AF: 0.0565 AC: 2239 AN: 39624

South Asian (SAS) AF: 0.0221 AC: 1905 AN: 86090

European-Finnish (FIN) AF: 0.00150 AC: 80 AN: 53402

Middle Eastern (MID) AF: 0.0144 AC: 83 AN: 5760

European-Non Finnish (NFE) AF: 0.00394 AC: 4360 AN: 1106528

Other (OTH) AF: 0.0144 AC: 867 AN: 60208

GnomAD4 genome AF: 0.0158 AC: 2410 AN: 152248 Hom.: 57 Cov.: 32 AF XY: 0.0161 AC XY: 1200 AN XY: 74436

African (AFR) AF: 0.0346 AC: 1435 AN: 41528

American (AMR) AF: 0.00621 AC: 95 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0839 AC: 434 AN: 5172

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4822

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00398 AC: 271 AN: 68030

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0109 Hom.: 31

Bravo AF: 0.0169

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11568637; hg19: chr13-95886854; COSMIC: COSV65314044;