13-51933584-C-T

Variant names:

• chr13-51933584-C-T
• rs1051332
• ENST00000634810.1:n.4915G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000634810.1(ATP7B):​n.4915G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,128 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11321 hom., cov: 32)
  • Exomes 𝑓: 0.56 (4 hom.)
• Consequence: ATP7B ENST00000634810.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 17 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]

TMEM272 (HGNC:26737): (transmembrane protein 272) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-51933584-C-T is Benign according to our data. Variant chr13-51933584-C-T is described in ClinVar as Benign. ClinVar VariationId is 312357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.*1172G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.*1172G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54127 AN: 151992 Hom.: 11325 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 4 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.356 AC: 54121 AN: 152110 Hom.: 11321 Cov.: 32 AF XY: 0.357 AC XY: 26532 AN XY: 74340

African (AFR) AF: 0.121 AC: 5044 AN: 41528

American (AMR) AF: 0.376 AC: 5747 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1394 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5170

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4822

European-Finnish (FIN) AF: 0.473 AC: 4994 AN: 10556

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

European-Non Finnish (NFE) AF: 0.472 AC: 32109 AN: 67960

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.425 Hom.: 30067

Bravo AF: 0.342

Asia WGS AF: 0.363 AC: 1258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wilson disease Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.48
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1051332; hg19: chr13-52507720; COSMIC: COSV54444834; COSMIC: COSV54444834;