chr13-95028031-G-A

Variant names:

• chr13-95028031-G-A
• rs4148546
• NM_005845.5:c.3871-6349C>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.3871-6349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,912 control chromosomes in the GnomAD database, including 23,448 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 0.55 (23448 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3871-6349C>T		intron_variant	Intron 30 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3730-6349C>T		intron_variant	Intron 29 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.3742-6349C>T		intron_variant	Intron 30 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.3322-6349C>T		intron_variant	Intron 27 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3871-6349C>T		intron_variant	Intron 30 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83481 AN: 151794 Hom.: 23415 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.550 AC: 83556 AN: 151912 Hom.: 23448 Cov.: 32 AF XY: 0.552 AC XY: 41011 AN XY: 74236

African (AFR) AF: 0.658 AC: 27287 AN: 41440

American (AMR) AF: 0.445 AC: 6786 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2546 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2423 AN: 4810

European-Finnish (FIN) AF: 0.625 AC: 6592 AN: 10544

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34615 AN: 67926

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.516 Hom.: 59117

Bravo AF: 0.536

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.20
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: rs4148546; hg19: chr13-95680285;