chr13-95226588-G-A

Variant names:

• chr13-95226588-G-A
• rs4636781
• NM_005845.5:c.531+8022C>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.531+8022C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,616 control chromosomes in the GnomAD database, including 44,753 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 0.76 (44753 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.531+8022C>T		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+8022C>T		intron_variant	Intron 4 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115809 AN: 151494 Hom.: 44728 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.764 AC: 115883 AN: 151616 Hom.: 44753 Cov.: 32 AF XY: 0.757 AC XY: 56117 AN XY: 74102

African (AFR) AF: 0.671 AC: 27695 AN: 41286

American (AMR) AF: 0.753 AC: 11474 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2463 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3469 AN: 5138

South Asian (SAS) AF: 0.690 AC: 3324 AN: 4814

European-Finnish (FIN) AF: 0.795 AC: 8366 AN: 10526

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.835 AC: 56652 AN: 67848

Other (OTH) AF: 0.751 AC: 1581 AN: 2106

Alfa AF: 0.812 Hom.: 58677

Bravo AF: 0.757

Asia WGS AF: 0.688 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		0.028
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: rs4636781; hg19: chr13-95878842;