chr3-130894790-C-G

Variant names:

• chr3-130894790-C-G
• rs112703671
• NM_001378687.1:c.6+15C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0540

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ATP2C1	NM_001378687.1	c.6+15C>G		intron_variant	Intron 2 of 27	ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6	c.6+15C>G		intron_variant	Intron 2 of 27	5	NM_001378687.1	ENSP00000427461.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7531 AN: 152162 Hom.: 263 Cov.: 31

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

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

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

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

Submissions by phenotype

not provided Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

May 19, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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

Other links and lift over

dbSNP: rs112703671; hg19: chr3-130613634;