rs28362532

Variant names:

• chr13-52011745-A-G
• rs28362532
• NM_001406512.1:c.-143T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_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
• Publications: 7 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: Orphanet, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 13-52011745-A-G is Benign according to our data. Variant chr13-52011745-A-G is described in ClinVar as Benign. ClinVar VariationId is 538871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406512.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	NM_001406512.1		c.-143T>C		5_prime_UTR	Exon 1 of 22	NP_001393441.1	P35670-1
	ATP7B	NM_001406516.1		c.-143T>C		5_prime_UTR	Exon 1 of 22	NP_001393445.1	P35670-4
	ATP7B	NM_001406522.1		c.-143T>C		5_prime_UTR	Exon 1 of 22	NP_001393451.1	B7ZLR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000911501.1		c.-143T>C		5_prime_UTR	Exon 1 of 22	ENSP00000581560.1
	ATP7B	ENST00000873569.1		c.-408T>C		5_prime_UTR	Exon 1 of 21	ENSP00000543628.1
	ATP7B	ENST00000713659.1		c.-408T>C		5_prime_UTR	Exon 1 of 17	ENSP00000518961.1	A0AAQ5BGP2

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

African (AFR) AF: 0.0389 AC: 1617 AN: 41556

American (AMR) AF: 0.119 AC: 1825 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.0622 AC: 322 AN: 5174

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10624

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8387 AN: 68014

Other (OTH) AF: 0.107 AC: 227 AN: 2116

Alfa AF: 0.101 Hom.: 110

Bravo AF: 0.0948

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Wilson disease (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.55
PhyloP100		-0.18
PromoterAI		-0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs28362532; hg19: chr13-52585881;