rs8187707

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000392.5(ABCC2):c.4488C>T(p.His1496=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 1,614,080 control chromosomes in the GnomAD database, including 2,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 192 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2323 hom. )

Consequence

ABCC2
NM_000392.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.43

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 10-99850776-C-T is Benign according to our data. Variant chr10-99850776-C-T is described in ClinVar as [Benign]. Clinvar id is 298479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5 linkuse as main transcript	c.4488C>T	p.His1496=	synonymous_variant	31/32	ENST00000647814.1
ABCC2	XM_006717630.4 linkuse as main transcript	c.3792C>T	p.His1264=	synonymous_variant	26/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1 linkuse as main transcript	c.4488C>T	p.His1496=	synonymous_variant	31/32		NM_000392.5	P1
ABCC2	ENST00000648523.1 linkuse as main transcript	c.*329C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7154

AN:

152186

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0567

Gnomad OTH

AF:

0.0679

GnomAD3 exomes

AF:

0.0435

AC:

10925

AN:

251416

Hom.:

365

AF XY:

0.0443

AC XY:

6014

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.0347

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0566

Gnomad OTH exome

AF:

0.0606

GnomAD4 exome

AF:

0.0523

AC:

76500

AN:

1461776

Hom.:

2323

Cov.:

AF XY:

0.0518

AC XY:

37664

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0360

Gnomad4 AMR exome

AF:

0.0375

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0185

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.0567

Gnomad4 OTH exome

AF:

0.0583

GnomAD4 genome

AF:

0.0470

AC:

7165

AN:

152304

Hom.:

192

Cov.:

AF XY:

0.0452

AC XY:

3368

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0356

Gnomad4 AMR

AF:

0.0556

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0566

Gnomad4 OTH

AF:

0.0676

Alfa

AF:

0.0596

Hom.:

439

Bravo

AF:

0.0506

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0661

EpiControl

AF:

0.0727

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

ABCC2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 10, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Dubin-Johnson syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

8.2

Dann

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over