rs3740067

Positions:

• chr10-99844024-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000392.5(ABCC2):​c.3843+124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 913,174 control chromosomes in the GnomAD database, including 55,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7705 hom., cov: 32)
  • Exomes 𝑓: 0.35 (47464 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.585

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-99844024-C-G is Benign according to our data. Variant chr10-99844024-C-G is described in ClinVar as [Benign]. Clinvar id is 1275707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.3843+124C>G		intron_variant		ENST00000647814.1	NP_000383.2
ABCC2	XM_006717630.4	c.3147+124C>G		intron_variant			XP_006717693.1
ABCC2	XR_945604.4	n.4048+124C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.3843+124C>G		intron_variant			NM_000392.5	ENSP00000497274.1
ABCC2	ENST00000649459.1	n.191+124C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46486 AN: 151976 Hom.: 7710 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.350 AC: 266338 AN: 761078 Hom.: 47464 AF XY: 0.350 AC XY: 141379 AN XY: 403498

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.306 AC: 46498 AN: 152096 Hom.: 7705 Cov.: 32 AF XY: 0.306 AC XY: 22715 AN XY: 74330

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.333

Alfa AF: 0.338 Hom.: 1321

Bravo AF: 0.300

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.56

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: rs3740067; hg19: chr10-101603781; COSMIC: COSV64988729;