3-130894557-C-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001378687.1(ATP2C1):c.-180-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,425,194 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0054 ( 24 hom. )
Consequence
ATP2C1
NM_001378687.1 intron
NM_001378687.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.675
Genes affected
ATP2C1 (HGNC:13211): (ATPase secretory pathway Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 3-130894557-C-A is Benign according to our data. Variant chr3-130894557-C-A is described in ClinVar as [Benign]. Clinvar id is 343313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00429 (653/152152) while in subpopulation NFE AF= 0.00669 (455/67982). AF 95% confidence interval is 0.00618. There are 2 homozygotes in gnomad4. There are 299 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 653 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP2C1 | NM_001378687.1 | c.-180-33C>A | intron_variant | ENST00000510168.6 | NP_001365616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP2C1 | ENST00000510168.6 | c.-180-33C>A | intron_variant | 5 | NM_001378687.1 | ENSP00000427461 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00430 AC: 653AN: 152034Hom.: 2 Cov.: 31
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GnomAD4 exome AF: 0.00537 AC: 6840AN: 1273042Hom.: 24 Cov.: 33 AF XY: 0.00546 AC XY: 3374AN XY: 617692
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GnomAD4 genome AF: 0.00429 AC: 653AN: 152152Hom.: 2 Cov.: 31 AF XY: 0.00402 AC XY: 299AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial benign pemphigus Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at