NM_000053.4:c.2866-13G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000053.4(ATP7B):c.2866-13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,613,784 control chromosomes in the GnomAD database, including 4,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1277 hom., cov: 33)

Exomes 𝑓: 0.053 ( 2862 hom. )

Consequence

ATP7B
NM_000053.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.286

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Wilson disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ATP7B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 13-51946491-C-G is Benign according to our data. Variant chr13-51946491-C-G is described in ClinVar as Benign. ClinVar VariationId is 35709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4 link	c.2866-13G>C		intron_variant	Intron 12 of 20	ENST00000242839.10	NP_000044.2	P35670-1B7ZLR4A0A024RDX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10 link	c.2866-13G>C		intron_variant	Intron 12 of 20	1	NM_000053.4	ENSP00000242839.5		P35670-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15560

AN:

152168

Hom.:

1279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0882

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.0394

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0480

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0852

GnomAD2 exomes

AF:

0.0693

AC:

17245

AN:

248860

AF XY:

0.0647

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0920

Gnomad EAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0700

GnomAD4 exome

AF:

0.0527

AC:

77064

AN:

1461498

Hom.:

2862

Cov.:

AF XY:

0.0522

AC XY:

37969

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.241

AC:

8053

AN:

33462

American (AMR)

AF:

0.0993

AC:

4436

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

2418

AN:

26130

East Asian (EAS)

AF:

0.0366

AC:

1451

AN:

39696

South Asian (SAS)

AF:

0.0573

AC:

4938

AN:

86200

European-Finnish (FIN)

AF:

0.0497

AC:

2653

AN:

53410

Middle Eastern (MID)

AF:

0.107

AC:

617

AN:

5750

European-Non Finnish (NFE)

AF:

0.0437

AC:

48577

AN:

1111790

Other (OTH)

AF:

0.0649

AC:

3921

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3935

7870

11804

15739

19674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1970

3940

5910

7880

9850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.102

AC:

15589

AN:

152286

Hom.:

1277

Cov.:

AF XY:

0.100

AC XY:

7473

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.232

AC:

9616

AN:

41530

American (AMR)

AF:

0.0883

AC:

1352

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

311

AN:

3470

East Asian (EAS)

AF:

0.0397

AC:

206

AN:

5186

South Asian (SAS)

AF:

0.0615

AC:

297

AN:

4828

European-Finnish (FIN)

AF:

0.0480

AC:

510

AN:

10614

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0453

AC:

3079

AN:

68034

Other (OTH)

AF:

0.0844

AC:

178

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

671

1342

2012

2683

3354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0730

Hom.:

113

Bravo

AF:

0.111

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 11, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 04, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Wilson disease

Benign:6

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Mar 29, 2019

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing;curation

- -

Feb 14, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.96

(source)

DANN

Benign

0.68

PhyloP100

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over