NM_000392.5:c.3258+801T>G

Variant names:

• chr10-99832932-T-G
• rs4148399
• NM_000392.5:c.3258+801T>G

Variant summary

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

The NM_000392.5(ABCC2):​c.3258+801T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,250 control chromosomes in the GnomAD database, including 664 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 0.072 (664 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	NM_000392.5	MANE Select	c.3258+801T>G		intron	N/A	NP_000383.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	ENST00000647814.1	MANE Select	c.3258+801T>G		intron	N/A	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10980 AN: 152132 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0723 AC: 11015 AN: 152250 Hom.: 664 Cov.: 32 AF XY: 0.0777 AC XY: 5783 AN XY: 74450

African (AFR) AF: 0.0644 AC: 2677 AN: 41542

American (AMR) AF: 0.0661 AC: 1011 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5172

South Asian (SAS) AF: 0.209 AC: 1010 AN: 4830

European-Finnish (FIN) AF: 0.0786 AC: 834 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3398 AN: 68016

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0580 Hom.: 556

Bravo AF: 0.0714

Asia WGS AF: 0.277 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.44
PhyloP100		0.35
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: rs4148399; hg19: chr10-101592689;