rs2182262

Positions:

• chr13-95039258-T-C
• chr13-95039258-T-G

Variant summary

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

The NM_005845.5(ABCC4):​c.3735+4424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,108 control chromosomes in the GnomAD database, including 50,227 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 0.81 (50227 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3735+4424A>G		intron_variant		ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3594+4424A>G		intron_variant			NP_001288758.1
ABCC4	XM_047430034.1	c.3606+4424A>G		intron_variant			XP_047285990.1
ABCC4	XM_047430035.1	c.3186+4424A>G		intron_variant			XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3735+4424A>G		intron_variant			NM_005845.5	ENSP00000494609	P1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123012 AN: 151992 Hom.: 50191 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123107 AN: 152108 Hom.: 50227 Cov.: 31 AF XY: 0.811 AC XY: 60331 AN XY: 74378

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.818

Alfa AF: 0.841 Hom.: 39686

Bravo AF: 0.804

Asia WGS AF: 0.757 AC: 2631 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.45
DANN	Benign	0.31

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: rs2182262; hg19: chr13-95691512;