NM_000392.5:c.1530+806C>T

Variant names:

• chr10-99806253-C-T
• rs11190291
• NM_000392.5:c.1530+806C>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.1530+806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,096 control chromosomes in the GnomAD database, including 2,735 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 (2735 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.1530+806C>T		intron_variant	Intron 11 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.1530+806C>T		intron_variant	Intron 11 of 31		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28312 AN: 151978 Hom.: 2739 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.186 AC: 28310 AN: 152096 Hom.: 2735 Cov.: 32 AF XY: 0.183 AC XY: 13599 AN XY: 74356

African (AFR) AF: 0.183 AC: 7587 AN: 41474

American (AMR) AF: 0.159 AC: 2426 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3466

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5180

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4810

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10566

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13542 AN: 68008

Other (OTH) AF: 0.193 AC: 408 AN: 2114

Alfa AF: 0.199 Hom.: 1759

Bravo AF: 0.186

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		0.36
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: rs11190291; hg19: chr10-101566010;