Variant NM_000053.4:c.1544-53A>C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000053.4(ATP7B):c.1544-53A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,598,864 control chromosomes in the GnomAD database, including 387,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36326 hom., cov: 30)

Exomes 𝑓: 0.69 ( 351512 hom. )

Consequence

ATP7B
NM_000053.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

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:

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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 13-51968660-T-G is Benign according to our data. Variant chr13-51968660-T-G is described in ClinVar as [Benign]. Clinvar id is 676098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4 link	c.1544-53A>C		intron_variant	Intron 3 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.1544-53A>C		intron_variant	Intron 3 of 20	1	NM_000053.4	ENSP00000242839.5		P35670-1

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104539

AN:

151754

Hom.:

36289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.713

GnomAD4 exome

AF:

0.694

AC:

1003998

AN:

1446992

Hom.:

351512

AF XY:

0.689

AC XY:

496490

AN XY:

720834

show subpopulations

Gnomad4 AFR exome

AF:

0.693

Gnomad4 AMR exome

AF:

0.638

Gnomad4 ASJ exome

AF:

0.658

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.511

Gnomad4 FIN exome

AF:

0.716

Gnomad4 NFE exome

AF:

0.718

Gnomad4 OTH exome

AF:

0.690

GnomAD4 genome

AF:

0.689

AC:

104630

AN:

151872

Hom.:

36326

Cov.:

AF XY:

0.685

AC XY:

50798

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.678

Gnomad4 ASJ

AF:

0.659

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.499

Gnomad4 FIN

AF:

0.721

Gnomad4 NFE

AF:

0.716

Gnomad4 OTH

AF:

0.714

Alfa

AF:

0.704

Hom.:

34357

Bravo

AF:

0.687

Asia WGS

AF:

0.546

AC:

1895

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wilson disease

Benign:2

Jan 30, 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: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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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