rs1189429

Variant names:

• chr13-95127715-G-A
• rs1189429
• NM_005845.5:c.2456-11714C>T

Variant summary

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

The ENST00000645237.2(ABCC4):​c.2456-11714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,938 control chromosomes in the GnomAD database, including 18,827 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 0.49 (18827 hom., cov: 32)
• Consequence: ABCC4 ENST00000645237.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645237.2. 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.2456-11714C>T		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.2315-11714C>T		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.2456-11714C>T		intron	N/A	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2456-11714C>T		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.2456-11714C>T		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.2315-11714C>T		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74186 AN: 151820 Hom.: 18819 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.489 AC: 74226 AN: 151938 Hom.: 18827 Cov.: 32 AF XY: 0.499 AC XY: 37032 AN XY: 74240

African (AFR) AF: 0.362 AC: 14996 AN: 41448

American (AMR) AF: 0.562 AC: 8580 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2606 AN: 5148

South Asian (SAS) AF: 0.684 AC: 3295 AN: 4814

European-Finnish (FIN) AF: 0.616 AC: 6488 AN: 10532

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.521 AC: 35375 AN: 67938

Other (OTH) AF: 0.478 AC: 1011 AN: 2114

Alfa AF: 0.504 Hom.: 32191

Bravo AF: 0.475

Asia WGS AF: 0.574 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.029
DANN	Benign	0.23
PhyloP100		-1.6
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: rs1189429; hg19: chr13-95779969;