rs11595888

Variant names:

• chr10-99827812-C-T
• rs11595888
• NM_000392.5:c.2621-2495C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000392.5(ABCC2):​c.2621-2495C>T variant causes a intron change. The variant allele was found at a frequency of 0.189 in 145,164 control chromosomes in the GnomAD database, including 2,709 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 0.19 (2709 hom., cov: 22)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	NM_000392.5	MANE Select	c.2621-2495C>T		intron	N/A	NP_000383.2	Q92887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	ENST00000647814.1	MANE Select	c.2621-2495C>T		intron	N/A	ENSP00000497274.1	Q92887

Frequencies

GnomAD3 genomes AF: 0.189 AC: 27436 AN: 145040 Hom.: 2714 Cov.: 22

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.189 AC: 27438 AN: 145164 Hom.: 2709 Cov.: 22 AF XY: 0.185 AC XY: 13024 AN XY: 70298

African (AFR) AF: 0.197 AC: 7686 AN: 38936

American (AMR) AF: 0.159 AC: 2272 AN: 14294

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 716 AN: 3412

East Asian (EAS) AF: 0.0915 AC: 442 AN: 4828

South Asian (SAS) AF: 0.261 AC: 1134 AN: 4348

European-Finnish (FIN) AF: 0.154 AC: 1478 AN: 9590

Middle Eastern (MID) AF: 0.194 AC: 54 AN: 278

European-Non Finnish (NFE) AF: 0.198 AC: 13159 AN: 66618

Other (OTH) AF: 0.197 AC: 390 AN: 1976

Alfa AF: 0.183 Hom.: 1018

Bravo AF: 0.193

Asia WGS AF: 0.164 AC: 572 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11595888; hg19: chr10-101587569;