13-95054859-T-C

Variant names:

• chr13-95054859-T-C
• rs1189446
• NM_005845.5:c.3367-1675A>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.3367-1675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,112 control chromosomes in the GnomAD database, including 40,694 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 0.72 (40694 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 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.3367-1675A>G		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.3226-1675A>G		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.3367-1675A>G		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3226-1675A>G		intron	N/A	ENSP00000494751.1
	ABCC4	ENST00000643051.1		n.*1277+711A>G		intron	N/A	ENSP00000495513.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108958 AN: 151994 Hom.: 40672 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.717 AC: 109020 AN: 152112 Hom.: 40694 Cov.: 32 AF XY: 0.718 AC XY: 53391 AN XY: 74366

African (AFR) AF: 0.486 AC: 20158 AN: 41476

American (AMR) AF: 0.809 AC: 12371 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2715 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3831 AN: 5172

South Asian (SAS) AF: 0.818 AC: 3943 AN: 4822

European-Finnish (FIN) AF: 0.758 AC: 8031 AN: 10590

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55432 AN: 67986

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.791 Hom.: 34756

Bravo AF: 0.709

Asia WGS AF: 0.767 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-2.2
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: rs1189446; hg19: chr13-95707113;