13-52011412-G-T

Variant summary

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

The NM_000053.4(ATP7B):​c.-75C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,603,372 control chromosomes in the GnomAD database, including 365,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27561 hom., cov: 34)
Exomes 𝑓: 0.68 ( 337517 hom. )

Consequence

ATP7B
NM_000053.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.36
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]

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=-0.77).
BP6
Variant 13-52011412-G-T is Benign according to our data. Variant chr13-52011412-G-T is described in ClinVar as [Benign]. Clinvar id is 312405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-52011412-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP7BNM_000053.4 linkc.-75C>A 5_prime_UTR_variant Exon 1 of 21 ENST00000242839.10 NP_000044.2 P35670-1B7ZLR4A0A024RDX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP7BENST00000242839.10 linkc.-75C>A 5_prime_UTR_variant Exon 1 of 21 1 NM_000053.4 ENSP00000242839.5 P35670-1

Frequencies

GnomAD3 genomes
AF:
0.577
AC:
87665
AN:
151958
Hom.:
27555
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.304
Gnomad AMI
AF:
0.550
Gnomad AMR
AF:
0.647
Gnomad ASJ
AF:
0.642
Gnomad EAS
AF:
0.595
Gnomad SAS
AF:
0.539
Gnomad FIN
AF:
0.705
Gnomad MID
AF:
0.665
Gnomad NFE
AF:
0.703
Gnomad OTH
AF:
0.638
GnomAD4 exome
AF:
0.678
AC:
983477
AN:
1451296
Hom.:
337517
Cov.:
28
AF XY:
0.675
AC XY:
487811
AN XY:
722498
show subpopulations
Gnomad4 AFR exome
AF:
0.289
Gnomad4 AMR exome
AF:
0.660
Gnomad4 ASJ exome
AF:
0.634
Gnomad4 EAS exome
AF:
0.564
Gnomad4 SAS exome
AF:
0.545
Gnomad4 FIN exome
AF:
0.700
Gnomad4 NFE exome
AF:
0.705
Gnomad4 OTH exome
AF:
0.663
GnomAD4 genome
AF:
0.577
AC:
87687
AN:
152076
Hom.:
27561
Cov.:
34
AF XY:
0.578
AC XY:
42971
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.304
Gnomad4 AMR
AF:
0.646
Gnomad4 ASJ
AF:
0.642
Gnomad4 EAS
AF:
0.595
Gnomad4 SAS
AF:
0.539
Gnomad4 FIN
AF:
0.705
Gnomad4 NFE
AF:
0.703
Gnomad4 OTH
AF:
0.640
Alfa
AF:
0.616
Hom.:
5759
Bravo
AF:
0.564
Asia WGS
AF:
0.560
AC:
1945
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Wilson disease Benign:5
Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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

- -

Mar 08, 2022
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 13, 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. -

Jul 14, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:4
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Dec 18, 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. -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Congenital disorder of glycosylation Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
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
-0.77
CADD
Benign
4.1
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs2277448; hg19: chr13-52585548; COSMIC: COSV54445614; COSMIC: COSV54445614; API