NM_000053.4:c.51+12001C>T

Variant names:

• chr13-51999286-G-A
• rs9535828
• NM_000053.4:c.51+12001C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000053.4(ATP7B):​c.51+12001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,934 control chromosomes in the GnomAD database, including 14,312 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 0.41 (14312 hom., cov: 31)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 13 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: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.51+12001C>T		intron_variant	Intron 1 of 20	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.51+12001C>T		intron_variant	Intron 1 of 20	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61864 AN: 151818 Hom.: 14315 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.407 AC: 61860 AN: 151934 Hom.: 14312 Cov.: 31 AF XY: 0.408 AC XY: 30330 AN XY: 74254

African (AFR) AF: 0.168 AC: 6974 AN: 41444

American (AMR) AF: 0.408 AC: 6235 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1568 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2517 AN: 5152

South Asian (SAS) AF: 0.344 AC: 1655 AN: 4814

European-Finnish (FIN) AF: 0.547 AC: 5768 AN: 10538

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35650 AN: 67940

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.489 Hom.: 43858

Bravo AF: 0.390

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.082
DANN	Benign	0.75
PhyloP100		-2.8
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: rs9535828; hg19: chr13-52573422;