13-95065652-T-C

Variant names:

• chr13-95065652-T-C
• rs1678387
• NM_005845.5:c.3211-2793A>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.3211-2793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,244 control chromosomes in the GnomAD database, including 66,540 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 0.93 (66540 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.3211-2793A>G		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.3070-2793A>G		intron	N/A	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3211-2793A>G		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.3211-2793A>G		intron	N/A	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.3208-2793A>G		intron	N/A	ENSP00000637480.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142121 AN: 152126 Hom.: 66488 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.934 AC: 142230 AN: 152244 Hom.: 66540 Cov.: 31 AF XY: 0.932 AC XY: 69396 AN XY: 74444

African (AFR) AF: 0.916 AC: 38041 AN: 41544

American (AMR) AF: 0.940 AC: 14382 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3344 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4090 AN: 5176

South Asian (SAS) AF: 0.945 AC: 4548 AN: 4812

European-Finnish (FIN) AF: 0.917 AC: 9725 AN: 10600

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64973 AN: 68032

Other (OTH) AF: 0.946 AC: 1993 AN: 2106

Alfa AF: 0.946 Hom.: 179542

Bravo AF: 0.935

Asia WGS AF: 0.868 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.86
PhyloP100		-0.0060
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: rs1678387; hg19: chr13-95717906;