rs899494

chr13-95209550-A-Gchr13-95209550-A-T

Variant summary

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

The NM_005845.5(ABCC4):c.669T>C(p.Ile223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,613,874 control chromosomes in the GnomAD database, including 583,998 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 0.83 (52727 hom., cov: 34)
  • Exomes 𝑓: 0.85 (531271 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.81).
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.669T>C	p.Ile223=	synonymous_variant	6/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.669T>C	p.Ile223=	synonymous_variant	6/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126405 AN: 152102 Hom.: 52705 Cov.: 34

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.816

GnomAD3 exomes AF: 0.833 AC: 209004 AN: 251008 Hom.: 87519 AF XY: 0.826 AC XY: 112107 AN XY: 135652

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.883

Gnomad ASJ exome AF: 0.736

Gnomad EAS exome AF: 0.788

Gnomad SAS exome AF: 0.742

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.859

Gnomad OTH exome AF: 0.825

GnomAD4 exome AF: 0.852 AC: 1244618 AN: 1461654 Hom.: 531271 Cov.: 47 AF XY: 0.848 AC XY: 616386 AN XY: 727132

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.877

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.748

Gnomad4 FIN exome AF: 0.852

Gnomad4 NFE exome AF: 0.867

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.831 AC: 126473 AN: 152220 Hom.: 52727 Cov.: 34 AF XY: 0.828 AC XY: 61608 AN XY: 74450

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.809

Alfa AF: 0.845 Hom.: 94857

Bravo AF: 0.830

Asia WGS AF: 0.773 AC: 2690 AN: 3478

EpiCase AF: 0.848

EpiControl AF: 0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.34
Dann	Benign	0.58
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: rs899494; hg19: chr13-95861804; COSMIC: COSV65316381;