rs943290

Variant names:

• chr13-95078804-G-A
• rs943290
• NM_005845.5:c.2687-3253C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95078804-G-A
• chr13-95078804-G-T

Variant summary

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

The NM_005845.5(ABCC4):​c.2687-3253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,024 control chromosomes in the GnomAD database, including 33,359 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 0.64 (33359 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.2687-3253C>T		intron_variant	Intron 21 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.2546-3253C>T		intron_variant	Intron 20 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.2558-3253C>T		intron_variant	Intron 21 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.2138-3253C>T		intron_variant	Intron 18 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.2687-3253C>T		intron_variant	Intron 21 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98015 AN: 151906 Hom.: 33359 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.645 AC: 98048 AN: 152024 Hom.: 33359 Cov.: 32 AF XY: 0.652 AC XY: 48422 AN XY: 74316

African (AFR) AF: 0.414 AC: 17161 AN: 41444

American (AMR) AF: 0.761 AC: 11634 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2900 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2687 AN: 5160

South Asian (SAS) AF: 0.815 AC: 3919 AN: 4806

European-Finnish (FIN) AF: 0.747 AC: 7898 AN: 10576

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49444 AN: 67968

Other (OTH) AF: 0.714 AC: 1506 AN: 2110

Alfa AF: 0.717 Hom.: 66141

Bravo AF: 0.634

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		0.31
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: rs943290; hg19: chr13-95731058;