13-51991990-T-G

Variant names:

• chr13-51991990-T-G
• rs9535826
• NM_000053.4:c.52-16822A>C

Variant summary

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

The NM_000053.4(ATP7B):​c.52-16822A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,026 control chromosomes in the GnomAD database, including 14,792 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 0.41 (14792 hom., cov: 31)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 8 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: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000309371 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.52-16822A>C		intron_variant	Intron 1 of 20	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.52-16822A>C		intron_variant	Intron 1 of 20	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63017 AN: 151908 Hom.: 14797 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.414 AC: 63013 AN: 152026 Hom.: 14792 Cov.: 31 AF XY: 0.417 AC XY: 30958 AN XY: 74308

African (AFR) AF: 0.176 AC: 7307 AN: 41498

American (AMR) AF: 0.411 AC: 6276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2743 AN: 5166

South Asian (SAS) AF: 0.359 AC: 1730 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 6021 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35849 AN: 67944

Other (OTH) AF: 0.465 AC: 981 AN: 2110

Alfa AF: 0.490 Hom.: 25926

Bravo AF: 0.396

Asia WGS AF: 0.419 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.11
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

Other links and lift over

dbSNP: rs9535826; hg19: chr13-52566126;