3-130894790-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378687.1(ATP2C1):​c.6+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,613,022 control chromosomes in the GnomAD database, including 4,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 263 hom., cov: 31)
Exomes 𝑓: 0.069 ( 3863 hom. )

Consequence

ATP2C1
NM_001378687.1 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0540
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 3-130894790-C-G is Benign according to our data. Variant chr3-130894790-C-G is described in ClinVar as [Benign]. Clinvar id is 343317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP2C1NM_001378687.1 linkuse as main transcriptc.6+15C>G intron_variant ENST00000510168.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP2C1ENST00000510168.6 linkuse as main transcriptc.6+15C>G intron_variant 5 NM_001378687.1 P3P98194-1

Frequencies

GnomAD3 genomes
AF:
0.0495
AC:
7531
AN:
152162
Hom.:
263
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0132
Gnomad AMI
AF:
0.00769
Gnomad AMR
AF:
0.0457
Gnomad ASJ
AF:
0.0383
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0186
Gnomad FIN
AF:
0.0644
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0772
Gnomad OTH
AF:
0.0498
GnomAD3 exomes
AF:
0.0500
AC:
12568
AN:
251414
Hom.:
423
AF XY:
0.0505
AC XY:
6866
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.0119
Gnomad AMR exome
AF:
0.0302
Gnomad ASJ exome
AF:
0.0396
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0198
Gnomad FIN exome
AF:
0.0635
Gnomad NFE exome
AF:
0.0759
Gnomad OTH exome
AF:
0.0513
GnomAD4 exome
AF:
0.0685
AC:
100133
AN:
1460742
Hom.:
3863
Cov.:
32
AF XY:
0.0673
AC XY:
48877
AN XY:
726786
show subpopulations
Gnomad4 AFR exome
AF:
0.0107
Gnomad4 AMR exome
AF:
0.0312
Gnomad4 ASJ exome
AF:
0.0382
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0205
Gnomad4 FIN exome
AF:
0.0640
Gnomad4 NFE exome
AF:
0.0797
Gnomad4 OTH exome
AF:
0.0576
GnomAD4 genome
AF:
0.0494
AC:
7530
AN:
152280
Hom.:
263
Cov.:
31
AF XY:
0.0478
AC XY:
3557
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0131
Gnomad4 AMR
AF:
0.0455
Gnomad4 ASJ
AF:
0.0383
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0188
Gnomad4 FIN
AF:
0.0644
Gnomad4 NFE
AF:
0.0772
Gnomad4 OTH
AF:
0.0497
Alfa
AF:
0.0597
Hom.:
67
Bravo
AF:
0.0467
Asia WGS
AF:
0.00751
AC:
26
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 19, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Familial benign pemphigus Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
14
DANN
Benign
0.65

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112703671; hg19: chr3-130613634; API