chr13-95299339-T-C

Variant names:

• chr13-95299339-T-C
• rs17189561
• NM_005845.5:c.74+1902A>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.74+1902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,606 control chromosomes in the GnomAD database, including 1,307 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 0.12 (1307 hom., cov: 30)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.74+1902A>G		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.74+1902A>G		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.74+1902A>G		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.74+1902A>G		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.74+1902A>G		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.74+1902A>G		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18290 AN: 151524 Hom.: 1305 Cov.: 30

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.121 AC: 18291 AN: 151606 Hom.: 1307 Cov.: 30 AF XY: 0.118 AC XY: 8703 AN XY: 74014

African (AFR) AF: 0.0579 AC: 2393 AN: 41326

American (AMR) AF: 0.120 AC: 1817 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5160

South Asian (SAS) AF: 0.0734 AC: 352 AN: 4798

European-Finnish (FIN) AF: 0.130 AC: 1359 AN: 10454

Middle Eastern (MID) AF: 0.184 AC: 53 AN: 288

European-Non Finnish (NFE) AF: 0.164 AC: 11145 AN: 67920

Other (OTH) AF: 0.144 AC: 301 AN: 2096

Alfa AF: 0.152 Hom.: 5217

Bravo AF: 0.118

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		0.50
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: rs17189561; hg19: chr13-95951593;