rs7325983

Variant names:

• chr13-51946491-C-G
• rs7325983
• NM_000053.4:c.2866-13G>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.2866-13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,613,784 control chromosomes in the GnomAD database, including 4,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1277 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2862 hom.)
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.286
• 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: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-51946491-C-G is Benign according to our data. Variant chr13-51946491-C-G is described in ClinVar as Benign. ClinVar VariationId is 35709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 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.2866-13G>C		intron	N/A	NP_000044.2
	ATP7B	NM_001406511.1		c.2866-13G>C		intron	N/A	NP_001393440.1
	ATP7B	NM_001406512.1		c.2866-13G>C		intron	N/A	NP_001393441.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000242839.10	TSL:1 MANE Select	c.2866-13G>C		intron	N/A	ENSP00000242839.5
	ATP7B	ENST00000634844.1	TSL:1	c.2722-13G>C		intron	N/A	ENSP00000489398.1
	ATP7B	ENST00000418097.7	TSL:1	c.2866-2200G>C		intron	N/A	ENSP00000393343.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15560 AN: 152168 Hom.: 1279 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0852

GnomAD2 exomes AF: 0.0693 AC: 17245 AN: 248860 AF XY: 0.0647

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0920

Gnomad EAS exome AF: 0.0463

Gnomad FIN exome AF: 0.0451

Gnomad NFE exome AF: 0.0463

Gnomad OTH exome AF: 0.0700

GnomAD4 exome AF: 0.0527 AC: 77064 AN: 1461498 Hom.: 2862 Cov.: 33 AF XY: 0.0522 AC XY: 37969 AN XY: 727018

African (AFR) AF: 0.241 AC: 8053 AN: 33462

American (AMR) AF: 0.0993 AC: 4436 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 2418 AN: 26130

East Asian (EAS) AF: 0.0366 AC: 1451 AN: 39696

South Asian (SAS) AF: 0.0573 AC: 4938 AN: 86200

European-Finnish (FIN) AF: 0.0497 AC: 2653 AN: 53410

Middle Eastern (MID) AF: 0.107 AC: 617 AN: 5750

European-Non Finnish (NFE) AF: 0.0437 AC: 48577 AN: 1111790

Other (OTH) AF: 0.0649 AC: 3921 AN: 60378

GnomAD4 genome AF: 0.102 AC: 15589 AN: 152286 Hom.: 1277 Cov.: 33 AF XY: 0.100 AC XY: 7473 AN XY: 74452

African (AFR) AF: 0.232 AC: 9616 AN: 41530

American (AMR) AF: 0.0883 AC: 1352 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.0397 AC: 206 AN: 5186

South Asian (SAS) AF: 0.0615 AC: 297 AN: 4828

European-Finnish (FIN) AF: 0.0480 AC: 510 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3079 AN: 68034

Other (OTH) AF: 0.0844 AC: 178 AN: 2110

Alfa AF: 0.0730 Hom.: 113

Bravo AF: 0.111

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	6	Wilson disease (6)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.96
DANN	Benign	0.68
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7325983; hg19: chr13-52520627;