rs1801247

Variant names:

• chr13-51946335-C-T
• rs1801247
• NM_000053.4:c.3009G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-51946335-C-T
• chr13-51946335-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000053.4(ATP7B):​c.3009G>A​(p.Ala1003Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,607,684 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (217 hom., cov: 33)
  • Exomes 𝑓: 0.058 (2819 hom.)
• Consequence: ATP7B NM_000053.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: -4.22
• 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]

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-51946335-C-T is Benign according to our data. Variant chr13-51946335-C-T is described in ClinVar as Benign. ClinVar VariationId is 35714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 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.3009G>A	p.Ala1003Ala	synonymous	Exon 13 of 21	NP_000044.2	P35670-1
	ATP7B	NM_001406511.1		c.3009G>A	p.Ala1003Ala	synonymous	Exon 14 of 22	NP_001393440.1	P35670-1
	ATP7B	NM_001406512.1		c.3009G>A	p.Ala1003Ala	synonymous	Exon 14 of 22	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.3009G>A	p.Ala1003Ala	synonymous	Exon 13 of 21	ENSP00000242839.5	P35670-1
	ATP7B	ENST00000634844.1	TSL:1	c.2865G>A	p.Ala955Ala	synonymous	Exon 13 of 21	ENSP00000489398.1	B7ZLR4
	ATP7B	ENST00000448424.7	TSL:1	c.2757G>A	p.Ala919Ala	synonymous	Exon 11 of 19	ENSP00000416738.3	E7ET55

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6500 AN: 152230 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.00916

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0549 AC: 13079 AN: 238048 AF XY: 0.0609

Gnomad AFR exome AF: 0.00674

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0717

Gnomad EAS exome AF: 0.00965

Gnomad FIN exome AF: 0.0763

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.0569

GnomAD4 exome AF: 0.0580 AC: 84356 AN: 1455336 Hom.: 2819 Cov.: 32 AF XY: 0.0601 AC XY: 43504 AN XY: 723460

African (AFR) AF: 0.00701 AC: 234 AN: 33386

American (AMR) AF: 0.0232 AC: 1019 AN: 43982

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 1890 AN: 26000

East Asian (EAS) AF: 0.00936 AC: 370 AN: 39530

South Asian (SAS) AF: 0.116 AC: 9862 AN: 85308

European-Finnish (FIN) AF: 0.0765 AC: 4049 AN: 52922

Middle Eastern (MID) AF: 0.0773 AC: 364 AN: 4706

European-Non Finnish (NFE) AF: 0.0570 AC: 63227 AN: 1109430

Other (OTH) AF: 0.0556 AC: 3341 AN: 60072

GnomAD4 genome AF: 0.0427 AC: 6503 AN: 152348 Hom.: 217 Cov.: 33 AF XY: 0.0441 AC XY: 3287 AN XY: 74494

African (AFR) AF: 0.00911 AC: 379 AN: 41596

American (AMR) AF: 0.0315 AC: 482 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5182

South Asian (SAS) AF: 0.113 AC: 545 AN: 4828

European-Finnish (FIN) AF: 0.0764 AC: 811 AN: 10616

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3837 AN: 68030

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0440 Hom.: 150

Bravo AF: 0.0356

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	7	Wilson disease (7)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs1801247; hg19: chr13-52520471; COSMIC: COSV54438365;