chr13-95251181-T-C

Variant names:

• chr13-95251181-T-C
• rs4148434
• NM_005845.5:c.75-3428A>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.75-3428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,930 control chromosomes in the GnomAD database, including 31,855 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 0.65 (31855 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.696 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.75-3428A>G		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.75-3428A>G		intron	N/A	NP_001288758.1	O15439-2
	ABCC4	NM_001105515.3		c.75-3428A>G		intron	N/A	NP_001098985.1	O15439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.75-3428A>G		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000629385.1	TSL:1	c.75-3428A>G		intron	N/A	ENSP00000487081.1	O15439-3
	ABCC4	ENST00000967420.1		c.75-3428A>G		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98196 AN: 151812 Hom.: 31841 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.647 AC: 98252 AN: 151930 Hom.: 31855 Cov.: 31 AF XY: 0.648 AC XY: 48119 AN XY: 74256

African (AFR) AF: 0.649 AC: 26855 AN: 41400

American (AMR) AF: 0.645 AC: 9856 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2439 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3686 AN: 5152

South Asian (SAS) AF: 0.684 AC: 3289 AN: 4810

European-Finnish (FIN) AF: 0.624 AC: 6575 AN: 10538

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43434 AN: 67980

Other (OTH) AF: 0.650 AC: 1371 AN: 2108

Alfa AF: 0.642 Hom.: 52308

Bravo AF: 0.647

Asia WGS AF: 0.680 AC: 2365 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	2.7
DANN	Benign	0.79
PhyloP100		0.011
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: rs4148434; hg19: chr13-95903435;