13-95193377-T-C

Variant names:

• chr13-95193377-T-C
• rs4148482
• NM_005845.5:c.1263+1459A>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.1263+1459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,084 control chromosomes in the GnomAD database, including 30,779 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 0.63 (30779 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1263+1459A>G		intron_variant	Intron 9 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1263+1459A>G		intron_variant	Intron 9 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96038 AN: 151966 Hom.: 30781 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.632 AC: 96069 AN: 152084 Hom.: 30779 Cov.: 32 AF XY: 0.628 AC XY: 46673 AN XY: 74330

African (AFR) AF: 0.546 AC: 22640 AN: 41502

American (AMR) AF: 0.604 AC: 9242 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2499 AN: 5140

South Asian (SAS) AF: 0.602 AC: 2896 AN: 4814

European-Finnish (FIN) AF: 0.711 AC: 7525 AN: 10590

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47225 AN: 67972

Other (OTH) AF: 0.607 AC: 1278 AN: 2106

Alfa AF: 0.671 Hom.: 15824

Bravo AF: 0.619

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.75
Mutation Taster		=100/0	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: rs4148482; hg19: chr13-95845631;