chr13-51950424-C-T

Variant names:

Variant summary

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

The NM_000053.4(ATP7B):c.2448-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,612,734 control chromosomes in the GnomAD database, including 163,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.36 ( 11416 hom., cov: 32)

Exomes 𝑓: 0.45 ( 151906 hom. )

Consequence

ATP7B
NM_000053.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.478

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 13-51950424-C-T is Benign according to our data. Variant chr13-51950424-C-T is described in ClinVar as [Benign]. Clinvar id is 254764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4 link	c.2448-25G>A		intron_variant	Intron 9 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.2448-25G>A		intron_variant	Intron 9 of 20	1	NM_000053.4	ENSP00000242839.5		P35670-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54354

AN:

152052

Hom.:

11419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.405

AC:

100851

AN:

249082

Hom.:

21544

AF XY:

0.409

AC XY:

55332

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.470

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.450

AC:

657117

AN:

1460564

Hom.:

151906

Cov.:

AF XY:

0.448

AC XY:

325423

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.357

AC:

54349

AN:

152170

Hom.:

11416

Cov.:

AF XY:

0.358

AC XY:

26659

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.425

Hom.:

2956

Bravo

AF:

0.343

Asia WGS

AF:

0.361

AC:

1251

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wilson disease

Benign:4

Jan 27, 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

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 20, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 14, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.3

DANN

Benign

0.63

BranchPoint Hunter

0.0

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