13-52010642-T-C

Position:

• chr13-52010642-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4	c.51+645A>G		intron_variant		ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10	c.51+645A>G		intron_variant		1	NM_000053.4	P1

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

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.683

Alfa AF: 0.685 Hom.: 7914

Bravo AF: 0.622

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.61

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: rs7321120; hg19: chr13-52584778;