rs4148386

Variant names:

• chr10-99788711-G-A
• rs4148386
• NM_000392.5:c.208-3523G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000392.5(ABCC2):​c.208-3523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 155,576 control chromosomes in the GnomAD database, including 25,551 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 0.57 (25239 hom., cov: 32)
  • Exomes 𝑓: 0.40 (312 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

NANOGP6 (HGNC:23104): (Nanog homeobox pseudogene 6)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• 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.208-3523G>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.208-3523G>A		intron_variant	Intron 2 of 31		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86975 AN: 151844 Hom.: 25229 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.403 AC: 1458 AN: 3614 Hom.: 312 Cov.: 0 AF XY: 0.410 AC XY: 946 AN XY: 2306

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.573 AC: 87032 AN: 151962 Hom.: 25239 Cov.: 32 AF XY: 0.577 AC XY: 42830 AN XY: 74248

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.539

Alfa AF: 0.565 Hom.: 31294

Bravo AF: 0.567

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs4148386; hg19: chr10-101548468;