chr10-99790154-G-A

Variant names:

• chr10-99790154-G-A
• rs4148389
• NM_000392.5:c.208-2080G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ABCC2 Gene-Disease associations (from GenCC):

• Dubin-Johnson syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.208-2080G>A		intron_variant	Intron 2 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.208-2080G>A		intron_variant	Intron 2 of 31		NM_000392.5	ENSP00000497274.1

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

African (AFR) AF: 0.563 AC: 23343 AN: 41436

American (AMR) AF: 0.566 AC: 8646 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1826 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3993 AN: 5184

South Asian (SAS) AF: 0.624 AC: 3015 AN: 4830

European-Finnish (FIN) AF: 0.636 AC: 6716 AN: 10562

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38861 AN: 67958

Other (OTH) AF: 0.545 AC: 1152 AN: 2112

Alfa AF: 0.575 Hom.: 14494

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
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148389; hg19: chr10-101549911;