13-51965390-T-G

Variant names:

• chr13-51965390-T-G
• rs9526814
• NM_000053.4:c.1708-357A>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.1708-357A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,938 control chromosomes in the GnomAD database, including 11,380 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 0.35 (11380 hom., cov: 32)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.1708-357A>C		intron_variant	Intron 4 of 20	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.1708-357A>C		intron_variant	Intron 4 of 20	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53538 AN: 151818 Hom.: 11381 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.352 AC: 53535 AN: 151938 Hom.: 11380 Cov.: 32 AF XY: 0.355 AC XY: 26337 AN XY: 74258

African (AFR) AF: 0.0982 AC: 4071 AN: 41462

American (AMR) AF: 0.378 AC: 5761 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1343 AN: 3464

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5168

South Asian (SAS) AF: 0.349 AC: 1675 AN: 4802

European-Finnish (FIN) AF: 0.475 AC: 5008 AN: 10542

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32229 AN: 67942

Other (OTH) AF: 0.416 AC: 872 AN: 2098

Alfa AF: 0.425 Hom.: 18378

Bravo AF: 0.336

Asia WGS AF: 0.393 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.13
PhyloP100		-0.14
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: rs9526814; hg19: chr13-52539526;