rs4148396

chr10-99832187-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000392.5(ABCC2):c.3258+56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,606,194 control chromosomes in the GnomAD database, including 310,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32450 hom., cov: 31)
  • Exomes 𝑓: 0.62 (278344 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.310

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-99832187-T-C is Benign according to our data. Variant chr10-99832187-T-C is described in ClinVar as [Benign]. Clinvar id is 1188977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5	c.3258+56T>C		intron_variant		ENST00000647814.1
ABCC2	XM_006717630.4	c.2562+56T>C		intron_variant
ABCC2	XM_047424598.1	c.3258+56T>C		intron_variant
ABCC2	XR_945604.4	n.3463+56T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1	c.3258+56T>C		intron_variant			NM_000392.5	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98805 AN: 151874 Hom.: 32438 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.617 AC: 897707 AN: 1454202 Hom.: 278344 AF XY: 0.617 AC XY: 446840 AN XY: 723754

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.642

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.775

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.650 AC: 98863 AN: 151992 Hom.: 32450 Cov.: 31 AF XY: 0.652 AC XY: 48428 AN XY: 74296

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.637

Alfa AF: 0.617 Hom.: 40548

Bravo AF: 0.655

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Dubin-Johnson syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.6
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4148396; hg19: chr10-101591944;