13-95194766-A-G

Position:

• chr13-95194766-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1263+70T>C		intron_variant		ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1263+70T>C		intron_variant			NM_005845.5	ENSP00000494609.1

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

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.485

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

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.471

Alfa AF: 0.470 Hom.: 22812

Bravo AF: 0.483

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274403; hg19: chr13-95847020; COSMIC: COSV65312179;