chr13-51937226-C-G

Variant names:

• chr13-51937226-C-G
• rs9535795
• NM_000053.4:c.4021+50G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.499

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.4021+50G>C		intron_variant	Intron 19 of 20	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.4021+50G>C		intron_variant	Intron 19 of 20	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85469 AN: 151626 Hom.: 24220 Cov.: 30

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

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.: 28 AF XY: 0.577 AC XY: 407071 AN XY: 705734

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.: 30 AF XY: 0.563 AC XY: 41754 AN XY: 74102

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Oct 10, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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PreventionGenetics, part of Exact Sciences

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Wilson disease Benign:1

Jul 01, 2021

Genome-Nilou Lab

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	-0.90
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

Other links and lift over

dbSNP: rs9535795; hg19: chr13-52511362; COSMIC: COSV54442967; COSMIC: COSV54442967;