13-52010642-T-C

Variant names:

• chr13-52010642-T-C
• rs7321120
• NM_000053.4:c.51+645A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000053.4(ATP7B):​c.51+645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,078 control chromosomes in the GnomAD database, including 32,233 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (32233 hom., cov: 33)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.84
• Publications: 4 publications found

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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	NM_000053.4	MANE Select	c.51+645A>G		intron	N/A	NP_000044.2	P35670-1
	ATP7B	NM_001406511.1		c.51+645A>G		intron	N/A	NP_001393440.1	P35670-1
	ATP7B	NM_001406512.1		c.51+645A>G		intron	N/A	NP_001393441.1	P35670-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000242839.10	TSL:1 MANE Select	c.51+645A>G		intron	N/A	ENSP00000242839.5	P35670-1
	ATP7B	ENST00000634844.1	TSL:1	c.51+645A>G		intron	N/A	ENSP00000489398.1	B7ZLR4
	ATP7B	ENST00000418097.7	TSL:1	c.51+645A>G		intron	N/A	ENSP00000393343.2	F5H748

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96338 AN: 151960 Hom.: 32217 Cov.: 33

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.682

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 96383 AN: 152078 Hom.: 32233 Cov.: 33 AF XY: 0.634 AC XY: 47174 AN XY: 74352

African (AFR) AF: 0.406 AC: 16831 AN: 41450

American (AMR) AF: 0.686 AC: 10487 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3074 AN: 5164

South Asian (SAS) AF: 0.554 AC: 2677 AN: 4828

European-Finnish (FIN) AF: 0.746 AC: 7897 AN: 10582

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.746 AC: 50687 AN: 67980

Other (OTH) AF: 0.683 AC: 1442 AN: 2112

Alfa AF: 0.688 Hom.: 13303

Bravo AF: 0.622

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.61
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7321120;

hg19: chr13-52584778;