rs9535795

chr13-51937226-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000053.4(ATP7B):c.4021+50G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,565,232 control chromosomes in the GnomAD database, including 262,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24230 hom., cov: 30)

Exomes 𝑓: 0.58 ( 238167 hom. )

Consequence

ATP7B
NM_000053.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.499

Variant links:

Genes affected

ATP7B (HGNC:870): (ATPase copper transporting beta) This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein is a monomer, and functions as a copper-transporting ATPase which exports copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease which is characterized by copper accumulation. [provided by RefSeq, Dec 2019]

ATP7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 13-51937226-C-G is Benign according to our data. Variant chr13-51937226-C-G is described in ClinVar as [Benign]. Clinvar id is 254770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-51937226-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4 linkuse as main transcript	c.4021+50G>C		intron_variant		ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10 linkuse as main transcript	c.4021+50G>C		intron_variant		1	NM_000053.4	P1	P35670-1

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85469

AN:

151626

Hom.:

24220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.651

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.566

AC:

140122

AN:

247424

Hom.:

40074

AF XY:

0.565

AC XY:

75844

AN XY:

134248

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.574

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.581

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.578

AC:

817418

AN:

1413492

Hom.:

238167

Cov.:

AF XY:

0.577

AC XY:

407071

AN XY:

705734

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.573

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.606

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.564

AC:

85523

AN:

151740

Hom.:

24230

Cov.:

AF XY:

0.563

AC XY:

41754

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.530

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.586

Alfa

AF:

0.576

Hom.:

4665

Bravo

AF:

0.563

Asia WGS

AF:

0.526

AC:

1824

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 10, 2016	- -

Wilson disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.82

Dann

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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