chr13-95234600-T-C

Position:

• chr13-95234600-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.531+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,607,928 control chromosomes in the GnomAD database, including 267 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 0.016 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (210 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.531+10A>G		intron_variant		ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.531+10A>G		intron_variant			NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2402 AN: 152130 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00398

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0145 AC: 3623 AN: 250690 Hom.: 127 AF XY: 0.0139 AC XY: 1882 AN XY: 135466

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.0966

Gnomad SAS exome AF: 0.0225

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00375

Gnomad OTH exome AF: 0.00753

GnomAD4 exome AF: 0.00743 AC: 10822 AN: 1455680 Hom.: 210 Cov.: 30 AF XY: 0.00776 AC XY: 5621 AN XY: 724682

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.0565

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.00394

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0158 AC: 2410 AN: 152248 Hom.: 57 Cov.: 32 AF XY: 0.0161 AC XY: 1200 AN XY: 74436

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00398

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0104 Hom.: 12

Bravo AF: 0.0169

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.1
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11568637; hg19: chr13-95886854; COSMIC: COSV65314044;