13-95073819-T-C

Variant names:

• chr13-95073819-T-C
• rs1189465
• NM_005845.5:c.2917+395A>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.2917+395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,962 control chromosomes in the GnomAD database, including 12,237 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 0.38 (12237 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.2917+395A>G		intron_variant	Intron 23 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.2776+395A>G		intron_variant	Intron 22 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.2788+395A>G		intron_variant	Intron 23 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.2368+395A>G		intron_variant	Intron 20 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.2917+395A>G		intron_variant	Intron 23 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57347 AN: 151844 Hom.: 12237 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.377 AC: 57354 AN: 151962 Hom.: 12237 Cov.: 32 AF XY: 0.388 AC XY: 28795 AN XY: 74270

African (AFR) AF: 0.171 AC: 7079 AN: 41448

American (AMR) AF: 0.466 AC: 7113 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2535 AN: 5148

South Asian (SAS) AF: 0.630 AC: 3030 AN: 4808

European-Finnish (FIN) AF: 0.511 AC: 5393 AN: 10560

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29362 AN: 67954

Other (OTH) AF: 0.429 AC: 904 AN: 2106

Alfa AF: 0.429 Hom.: 8735

Bravo AF: 0.362

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.21
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: rs1189465; hg19: chr13-95726073;