13-52012013-T-G

Variant names:

• chr13-52012013-T-G
• rs1021025464
• ENST00000911501.1:c.-411A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001406511.1(ATP7B):​c.-55+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000955 in 209,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ATP7B NM_001406511.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406511.1. 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_001406511.1		c.-55+7A>C		splice_region intron	N/A	NP_001393440.1	P35670-1
	ATP7B	NM_001406513.1		c.-55+7A>C		splice_region intron	N/A	NP_001393442.1
	ATP7B	NM_001406521.1		c.-55+7A>C		splice_region intron	N/A	NP_001393450.1	B7ZLR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000911501.1		c.-411A>C		5_prime_UTR	Exon 1 of 22	ENSP00000581560.1
	ATP7B	ENST00000873569.1		c.-676A>C		5_prime_UTR	Exon 1 of 21	ENSP00000543628.1
	ATP7B	ENST00000713659.1		c.-676A>C		5_prime_UTR	Exon 1 of 17	ENSP00000518961.1	A0AAQ5BGP2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000955 AC: 2 AN: 209360 Hom.: 0 Cov.: 0 AF XY: 0.00000893 AC XY: 1 AN XY: 111964

African (AFR) AF: 0.00 AC: 0 AN: 5824

American (AMR) AF: 0.00 AC: 0 AN: 8182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5712

East Asian (EAS) AF: 0.00 AC: 0 AN: 9476

South Asian (SAS) AF: 0.0000576 AC: 2 AN: 34752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 790

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 123268

Other (OTH) AF: 0.00 AC: 0 AN: 11122

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		3.0
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1021025464; hg19: chr13-52586149;