NM_001378687.1:c.531+4988A>G

Variant names:

• chr3-130946687-A-G
• rs2669858
• NM_001378687.1:c.531+4988A>G

Variant summary

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

The NM_001378687.1(ATP2C1):​c.531+4988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,254 control chromosomes in the GnomAD database, including 2,525 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 0.18 (2525 hom., cov: 32)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C1	NM_001378687.1	c.531+4988A>G		intron_variant	Intron 8 of 27	ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6	c.531+4988A>G		intron_variant	Intron 8 of 27	5	NM_001378687.1	ENSP00000427461.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26797 AN: 152136 Hom.: 2525 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.176 AC: 26808 AN: 152254 Hom.: 2525 Cov.: 32 AF XY: 0.170 AC XY: 12682 AN XY: 74458

African (AFR) AF: 0.183 AC: 7603 AN: 41534

American (AMR) AF: 0.143 AC: 2188 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 727 AN: 3472

East Asian (EAS) AF: 0.0449 AC: 233 AN: 5194

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1197 AN: 10608

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13179 AN: 68014

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.188 Hom.: 1504

Bravo AF: 0.179

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-2.5
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: rs2669858; hg19: chr3-130665531; COSMIC: COSV60754408;