13-95222702-T-C

Variant names:

• chr13-95222702-T-C
• rs1926657
• NM_005845.5:c.531+11908A>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+11908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,140 control chromosomes in the GnomAD database, including 45,401 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 0.77 (45401 hom., cov: 33)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 35 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.531+11908A>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+11908A>G		intron_variant	Intron 4 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116889 AN: 152022 Hom.: 45377 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 116961 AN: 152140 Hom.: 45401 Cov.: 33 AF XY: 0.762 AC XY: 56638 AN XY: 74360

African (AFR) AF: 0.685 AC: 28429 AN: 41502

American (AMR) AF: 0.754 AC: 11530 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2472 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3495 AN: 5156

South Asian (SAS) AF: 0.691 AC: 3334 AN: 4826

European-Finnish (FIN) AF: 0.796 AC: 8438 AN: 10594

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56806 AN: 67996

Other (OTH) AF: 0.754 AC: 1590 AN: 2110

Alfa AF: 0.810 Hom.: 188040

Bravo AF: 0.761

Asia WGS AF: 0.688 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.32
PhyloP100		-1.3
Mutation Taster		=99/1	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: rs1926657; hg19: chr13-95874956;