rs218498

Positions:

• chr3-130968073-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2C1	NM_001378687.1	c.1308+654C>T		intron_variant		ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6	c.1308+654C>T		intron_variant		5	NM_001378687.1	ENSP00000427461	P3

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

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.487

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.61

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: rs218498; hg19: chr3-130686917;