rs3740065

chr10-99845936-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000392.5(ABCC2):c.4146+154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,192 control chromosomes in the GnomAD database, including 2,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2029 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.675

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-99845936-A-G is Benign according to our data. Variant chr10-99845936-A-G is described in ClinVar as [Benign]. Clinvar id is 1181401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5	c.4146+154A>G		intron_variant		ENST00000647814.1
ABCC2	XM_006717630.4	c.3450+154A>G		intron_variant
ABCC2	XR_945604.4	n.4292+154A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1	c.4146+154A>G		intron_variant			NM_000392.5	P1
ABCC2	ENST00000648523.1	c.34+154A>G		intron_variant, NMD_transcript_variant
ABCC2	ENST00000649459.1	n.494+154A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23022 AN: 152074 Hom.: 2007 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.152 AC: 23089 AN: 152192 Hom.: 2029 Cov.: 32 AF XY: 0.154 AC XY: 11455 AN XY: 74392

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.150

Alfa AF: 0.122 Hom.: 2699

Bravo AF: 0.159

Asia WGS AF: 0.297 AC: 1029 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.95
Cadd	Benign	2.1
Dann	Benign	0.60

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: rs3740065; hg19: chr10-101605693;