rs1557070

chr13-95186749-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005845.5(ABCC4):c.1497C>T(p.Tyr499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,700 control chromosomes in the GnomAD database, including 2,563 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 0.073 (1299 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (1264 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.647 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.1497C>T	p.Tyr499=	synonymous_variant	11/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.1497C>T	p.Tyr499=	synonymous_variant	11/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11021 AN: 151886 Hom.: 1293 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.0548

GnomAD3 exomes AF: 0.0195 AC: 4906 AN: 251316 Hom.: 527 AF XY: 0.0144 AC XY: 1955 AN XY: 135836

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00704

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00830 AC: 12136 AN: 1461696 Hom.: 1264 Cov.: 31 AF XY: 0.00716 AC XY: 5205 AN XY: 727166

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.00827

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0727 AC: 11055 AN: 152004 Hom.: 1299 Cov.: 33 AF XY: 0.0697 AC XY: 5182 AN XY: 74294

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00176

Gnomad4 OTH AF: 0.0542

Alfa AF: 0.0200 Hom.: 502

Bravo AF: 0.0814

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	7.4
Dann	Benign	0.51

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: rs1557070; hg19: chr13-95839003; COSMIC: COSV65310726;