NM_000053.4:c.1286-610T>G

Variant names:

• chr13-51971359-A-C
• rs7999812
• NM_000053.4:c.1286-610T>G

Variant summary

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

The NM_000053.4(ATP7B):​c.1286-610T>G 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 152,106 control chromosomes in the GnomAD database, including 13,511 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 (13511 hom., cov: 32)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	NM_000053.4	MANE Select	c.1286-610T>G		intron	N/A	NP_000044.2
	ATP7B	NM_001406511.1		c.1286-610T>G		intron	N/A	NP_001393440.1
	ATP7B	NM_001406512.1		c.1286-610T>G		intron	N/A	NP_001393441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000242839.10	TSL:1 MANE Select	c.1286-610T>G		intron	N/A	ENSP00000242839.5
	ATP7B	ENST00000634844.1	TSL:1	c.1286-610T>G		intron	N/A	ENSP00000489398.1
	ATP7B	ENST00000418097.7	TSL:1	c.1286-610T>G		intron	N/A	ENSP00000393343.2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61887 AN: 151988 Hom.: 13513 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.407 AC: 61895 AN: 152106 Hom.: 13511 Cov.: 32 AF XY: 0.410 AC XY: 30449 AN XY: 74350

African (AFR) AF: 0.233 AC: 9656 AN: 41496

American (AMR) AF: 0.409 AC: 6251 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1489 AN: 3466

East Asian (EAS) AF: 0.487 AC: 2519 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4822

European-Finnish (FIN) AF: 0.528 AC: 5592 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33211 AN: 67970

Other (OTH) AF: 0.462 AC: 978 AN: 2116

Alfa AF: 0.459 Hom.: 21923

Bravo AF: 0.393

Asia WGS AF: 0.422 AC: 1461 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		0.11
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: rs7999812; hg19: chr13-52545495;