rs4148389

Positions:

• chr10-99790154-G-A
• chr10-99790154-G-C

Variant summary

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

The NM_000392.5(ABCC2):​c.208-2080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,034 control chromosomes in the GnomAD database, including 25,818 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 0.58 (25818 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

Genes affected

ABCC2 (HGNC:53): (ATP binding cassette subfamily C member 2) 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 protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5	c.208-2080G>A		intron_variant		ENST00000647814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1	c.208-2080G>A		intron_variant			NM_000392.5	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88055 AN: 151916 Hom.: 25805 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.580 AC: 88115 AN: 152034 Hom.: 25818 Cov.: 32 AF XY: 0.583 AC XY: 43376 AN XY: 74340

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.545

Alfa AF: 0.574 Hom.: 12323

Bravo AF: 0.575

Asia WGS AF: 0.657 AC: 2282 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.19

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: rs4148389; hg19: chr10-101549911;