rs28362532

Positions:

• chr13-52011745-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001406512.1(ATP7B):​c.-143T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 152,296 control chromosomes in the GnomAD database, including 772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.096 (772 hom., cov: 34)
• Consequence: ATP7B NM_001406512.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.185

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_001406512.1	c.-143T>C		5_prime_UTR_variant	1/22
ATP7B	NM_001406516.1	c.-143T>C		5_prime_UTR_variant	1/22
ATP7B	NM_001406522.1	c.-143T>C		5_prime_UTR_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000635406.1	n.106+275T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14633 AN: 152176 Hom.: 772 Cov.: 34

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.0961 AC: 14637 AN: 152296 Hom.: 772 Cov.: 34 AF XY: 0.0957 AC XY: 7127 AN XY: 74478

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0622

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.107

Alfa AF: 0.104 Hom.: 110

Bravo AF: 0.0948

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wilson disease Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 28, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28362532; hg19: chr13-52585881;