chr13-95045626-C-T

Variant names:

• chr13-95045626-C-T
• rs1151471
• NM_005845.5:c.3457-1188G>A

Variant summary

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

The NM_005845.5(ABCC4):​c.3457-1188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,000 control chromosomes in the GnomAD database, including 26,055 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 0.58 (26055 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.3457-1188G>A		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.3316-1188G>A		intron	N/A	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3457-1188G>A		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3316-1188G>A		intron	N/A	ENSP00000494751.1
	ABCC4	ENST00000471041.2	TSL:4	n.327-1188G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87679 AN: 151882 Hom.: 26033 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.577 AC: 87742 AN: 152000 Hom.: 26055 Cov.: 32 AF XY: 0.583 AC XY: 43273 AN XY: 74288

African (AFR) AF: 0.426 AC: 17673 AN: 41438

American (AMR) AF: 0.594 AC: 9064 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3803 AN: 5166

South Asian (SAS) AF: 0.747 AC: 3600 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6930 AN: 10562

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42874 AN: 67962

Other (OTH) AF: 0.589 AC: 1243 AN: 2112

Alfa AF: 0.611 Hom.: 47616

Bravo AF: 0.563

Asia WGS AF: 0.725 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		-0.24
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: rs1151471; hg19: chr13-95697880;