rs218498

Variant names:

• chr3-130968073-C-T
• rs218498
• NM_001378687.1:c.1308+654C>T

Variant summary

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

The NM_001378687.1(ATP2C1):​c.1308+654C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,978 control chromosomes in the GnomAD database, including 18,156 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 0.45 (18156 hom., cov: 32)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 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.1308+654C>T		intron	N/A	NP_001365616.1
	ATP2C1	NM_001378511.1		c.1410+654C>T		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.1410+654C>T		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.1308+654C>T		intron	N/A	ENSP00000427461.1
	ATP2C1	ENST00000359644.7	TSL:1	c.1308+654C>T		intron	N/A	ENSP00000352665.3
	ATP2C1	ENST00000422190.6	TSL:1	c.1308+654C>T		intron	N/A	ENSP00000402677.2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68225 AN: 151860 Hom.: 18162 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.449 AC: 68223 AN: 151978 Hom.: 18156 Cov.: 32 AF XY: 0.450 AC XY: 33414 AN XY: 74256

African (AFR) AF: 0.155 AC: 6413 AN: 41482

American (AMR) AF: 0.473 AC: 7219 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1967 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1427 AN: 5168

South Asian (SAS) AF: 0.547 AC: 2639 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6044 AN: 10526

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40849 AN: 67932

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.479 Hom.: 3777

Bravo AF: 0.423

Asia WGS AF: 0.378 AC: 1312 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.40
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: rs218498; hg19: chr3-130686917;