chr13-95075526-T-C

Position:

• chr13-95075526-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.2712A>G​(p.Leu904=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 1,613,966 control chromosomes in the GnomAD database, including 722,004 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 0.92 (64301 hom., cov: 31)
  • Exomes 𝑓: 0.95 (657703 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.64).
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.2712A>G	p.Leu904=	synonymous_variant	22/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.2571A>G	p.Leu857=	synonymous_variant	21/30
ABCC4	XM_047430034.1	c.2583A>G	p.Leu861=	synonymous_variant	22/31
ABCC4	XM_047430035.1	c.2163A>G	p.Leu721=	synonymous_variant	19/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.2712A>G	p.Leu904=	synonymous_variant	22/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139586 AN: 152040 Hom.: 64252 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.938

GnomAD3 exomes AF: 0.929 AC: 233219 AN: 251072 Hom.: 108633 AF XY: 0.934 AC XY: 126662 AN XY: 135658

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.929

Gnomad ASJ exome AF: 0.958

Gnomad EAS exome AF: 0.796

Gnomad SAS exome AF: 0.955

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.937

GnomAD4 exome AF: 0.948 AC: 1385421 AN: 1461808 Hom.: 657703 Cov.: 57 AF XY: 0.948 AC XY: 689599 AN XY: 727212

Gnomad4 AFR exome AF: 0.850

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.958

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.915

Gnomad4 NFE exome AF: 0.959

Gnomad4 OTH exome AF: 0.939

GnomAD4 genome AF: 0.918 AC: 139690 AN: 152158 Hom.: 64301 Cov.: 31 AF XY: 0.917 AC XY: 68234 AN XY: 74398

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.961

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.939

Alfa AF: 0.947 Hom.: 160386

Bravo AF: 0.916

Asia WGS AF: 0.869 AC: 3024 AN: 3476

EpiCase AF: 0.949

EpiControl AF: 0.954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.96
DANN	Benign	0.67
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: rs1678339; hg19: chr13-95727780; COSMIC: COSV65312135; COSMIC: COSV65312135;