NM_001378687.1:c.532-1648T>C

Variant names:

• chr3-130952173-T-C
• rs218492
• NM_001378687.1:c.532-1648T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378687.1(ATP2C1):​c.532-1648T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,176 control chromosomes in the GnomAD database, including 66,073 homozygotes. 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: 𝑓 0.93 (66073 hom., cov: 31)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 1 publications found

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]

ATP2C1 Gene-Disease associations (from GenCC):

• Hailey-Hailey disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378687.1	MANE Select	c.532-1648T>C		intron	N/A	NP_001365616.1
	ATP2C1	NM_001378511.1		c.634-1648T>C		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.634-1648T>C		intron	N/A	NP_001186109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000510168.6	TSL:5 MANE Select	c.532-1648T>C		intron	N/A	ENSP00000427461.1
	ATP2C1	ENST00000359644.7	TSL:1	c.532-1648T>C		intron	N/A	ENSP00000352665.3
	ATP2C1	ENST00000422190.6	TSL:1	c.532-1648T>C		intron	N/A	ENSP00000402677.2

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141473 AN: 152058 Hom.: 66019 Cov.: 31

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.922

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.930 AC: 141582 AN: 152176 Hom.: 66073 Cov.: 31 AF XY: 0.924 AC XY: 68713 AN XY: 74380

African (AFR) AF: 0.969 AC: 40257 AN: 41524

American (AMR) AF: 0.859 AC: 13110 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3105 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4084 AN: 5168

South Asian (SAS) AF: 0.910 AC: 4390 AN: 4826

European-Finnish (FIN) AF: 0.872 AC: 9236 AN: 10588

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64375 AN: 68012

Other (OTH) AF: 0.922 AC: 1947 AN: 2112

Alfa AF: 0.939 Hom.: 9615

Bravo AF: 0.930

Asia WGS AF: 0.829 AC: 2885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.74
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs218492; hg19: chr3-130671017;