rs2274405

chr13-95206724-T-C

Variant summary

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

The NM_005845.5(ABCC4):c.969A>G(p.Ser323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,613,838 control chromosomes in the GnomAD database, including 345,794 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 0.65 (32286 hom., cov: 32)
  • Exomes 𝑓: 0.65 (313508 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.42

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=-0.9).
• BP7: Synonymous conserved (PhyloP=-5.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.969A>G	p.Ser323=	synonymous_variant	8/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.969A>G	p.Ser323=	synonymous_variant	8/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98833 AN: 151904 Hom.: 32278 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.625

GnomAD3 exomes AF: 0.630 AC: 158274 AN: 251294 Hom.: 50389 AF XY: 0.631 AC XY: 85670 AN XY: 135814

Gnomad AFR exome AF: 0.696

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.527

Gnomad SAS exome AF: 0.639

Gnomad FIN exome AF: 0.633

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.628

GnomAD4 exome AF: 0.653 AC: 955257 AN: 1461816 Hom.: 313508 Cov.: 57 AF XY: 0.653 AC XY: 474787 AN XY: 727220

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.650 AC: 98877 AN: 152022 Hom.: 32286 Cov.: 32 AF XY: 0.644 AC XY: 47829 AN XY: 74298

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.619

Alfa AF: 0.648 Hom.: 66532

Bravo AF: 0.647

Asia WGS AF: 0.556 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.077
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2274405; hg19: chr13-95858978; COSMIC: COSV65309326;