13-95194766-A-G

Variant names:

• chr13-95194766-A-G
• rs2274403
• NM_005845.5:c.1263+70T>C

Variant summary

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

The NM_005845.5(ABCC4):​c.1263+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,317,414 control chromosomes in the GnomAD database, including 152,601 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 0.48 (17782 hom., cov: 32)
  • Exomes 𝑓: 0.48 (134819 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 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.1263+70T>C		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.1263+70T>C		intron	N/A	NP_001288758.1	O15439-2
	ABCC4	NM_001105515.3		c.1263+70T>C		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.1263+70T>C		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000629385.1	TSL:1	c.1263+70T>C		intron	N/A	ENSP00000487081.1	O15439-3
	ABCC4	ENST00000967420.1		c.1263+70T>C		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73372 AN: 151884 Hom.: 17781 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.480 AC: 559488 AN: 1165412 Hom.: 134819 AF XY: 0.479 AC XY: 279914 AN XY: 584936

African (AFR) AF: 0.489 AC: 13194 AN: 26960

American (AMR) AF: 0.488 AC: 17269 AN: 35422

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 10162 AN: 23182

East Asian (EAS) AF: 0.518 AC: 19012 AN: 36696

South Asian (SAS) AF: 0.437 AC: 31717 AN: 72646

European-Finnish (FIN) AF: 0.513 AC: 26219 AN: 51122

Middle Eastern (MID) AF: 0.462 AC: 2395 AN: 5184

European-Non Finnish (NFE) AF: 0.480 AC: 415186 AN: 864074

Other (OTH) AF: 0.485 AC: 24334 AN: 50126

GnomAD4 genome AF: 0.483 AC: 73409 AN: 152002 Hom.: 17782 Cov.: 32 AF XY: 0.482 AC XY: 35841 AN XY: 74288

African (AFR) AF: 0.486 AC: 20134 AN: 41398

American (AMR) AF: 0.470 AC: 7181 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3472

East Asian (EAS) AF: 0.512 AC: 2643 AN: 5166

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4814

European-Finnish (FIN) AF: 0.524 AC: 5534 AN: 10564

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32516 AN: 67994

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.472 Hom.: 28983

Bravo AF: 0.483

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		0.068
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: rs2274403; hg19: chr13-95847020; COSMIC: COSV65312179;