rs2147363

Variant names:

• chr13-51968660-T-G
• rs2147363
• NM_000053.4:c.1544-53A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-51968660-T-G
• chr13-51968660-T-A
• chr13-51968660-T-C

Variant summary

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

The NM_000053.4(ATP7B):​c.1544-53A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,598,864 control chromosomes in the GnomAD database, including 387,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36326 hom., cov: 30)
  • Exomes 𝑓: 0.69 (351512 hom.)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.38
• Publications: 20 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, Orphanet, 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=-0.9).
• BP6: Variant 13-51968660-T-G is Benign according to our data. Variant chr13-51968660-T-G is described in ClinVar as Benign. ClinVar VariationId is 676098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	NM_000053.4	MANE Select	c.1544-53A>C		intron	N/A	NP_000044.2	P35670-1
	ATP7B	NM_001406511.1		c.1544-53A>C		intron	N/A	NP_001393440.1	P35670-1
	ATP7B	NM_001406512.1		c.1544-53A>C		intron	N/A	NP_001393441.1	P35670-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000242839.10	TSL:1 MANE Select	c.1544-53A>C		intron	N/A	ENSP00000242839.5	P35670-1
	ATP7B	ENST00000634844.1	TSL:1	c.1544-53A>C		intron	N/A	ENSP00000489398.1	B7ZLR4
	ATP7B	ENST00000418097.7	TSL:1	c.1544-53A>C		intron	N/A	ENSP00000393343.2	F5H748

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104539 AN: 151754 Hom.: 36289 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.694 AC: 1003998 AN: 1446992 Hom.: 351512 AF XY: 0.689 AC XY: 496490 AN XY: 720834

African (AFR) AF: 0.693 AC: 22966 AN: 33150

American (AMR) AF: 0.638 AC: 28461 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 17144 AN: 26050

East Asian (EAS) AF: 0.480 AC: 19018 AN: 39618

South Asian (SAS) AF: 0.511 AC: 43872 AN: 85776

European-Finnish (FIN) AF: 0.716 AC: 38003 AN: 53092

Middle Eastern (MID) AF: 0.711 AC: 3424 AN: 4814

European-Non Finnish (NFE) AF: 0.718 AC: 789852 AN: 1100032

Other (OTH) AF: 0.690 AC: 41258 AN: 59836

GnomAD4 genome AF: 0.689 AC: 104630 AN: 151872 Hom.: 36326 Cov.: 30 AF XY: 0.685 AC XY: 50798 AN XY: 74188

African (AFR) AF: 0.690 AC: 28561 AN: 41414

American (AMR) AF: 0.678 AC: 10365 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2533 AN: 5122

South Asian (SAS) AF: 0.499 AC: 2399 AN: 4810

European-Finnish (FIN) AF: 0.721 AC: 7605 AN: 10544

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48625 AN: 67910

Other (OTH) AF: 0.714 AC: 1506 AN: 2110

Alfa AF: 0.703 Hom.: 45549

Bravo AF: 0.687

Asia WGS AF: 0.546 AC: 1895 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2147363; hg19: chr13-52542796; COSMIC: COSV54436234; COSMIC: COSV54436234;