chr13-51965390-T-G

Position:

• chr13-51965390-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• 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/exons	MANE	UniProt
ATP7B	NM_000053.4	c.1708-357A>C		intron_variant		ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10	c.1708-357A>C		intron_variant		1	NM_000053.4	P1

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

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.416

Alfa AF: 0.441 Hom.: 14455

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

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: rs9526814; hg19: chr13-52539526;