rs1316658

Variant names:

• chr3-130850713-T-G
• rs1316658
• NM_001378511.1:c.-108T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-130850713-T-G
• chr3-130850713-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378511.1(ATP2C1):​c.-108T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 507,568 control chromosomes in the GnomAD database, including 128,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41568 hom., cov: 33)
  • Exomes 𝑓: 0.70 (87269 hom.)
• Consequence: ATP2C1 NM_001378511.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• Publications: 12 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: Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000306101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-130850713-T-G is Benign according to our data. Variant chr3-130850713-T-G is described in ClinVar as Benign. ClinVar VariationId is 1262929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378511.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378511.1		c.-108T>G		5_prime_UTR	Exon 1 of 28	NP_001365440.1
	ATP2C1	NM_001199180.2		c.-108T>G		5_prime_UTR	Exon 1 of 28	NP_001186109.1	P98194-7
	ATP2C1	NM_001199181.3		c.-108T>G		5_prime_UTR	Exon 1 of 27	NP_001186110.1	B4E2Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000507488.6	TSL:2	c.-108T>G		5_prime_UTR	Exon 1 of 28	ENSP00000421326.3	P98194-7
	ATP2C1	ENST00000505330.5	TSL:2	c.-108T>G		5_prime_UTR	Exon 1 of 27	ENSP00000423774.2	B4E2Q0
	ATP2C1	ENST00000504381.5	TSL:2	c.-108T>G		5_prime_UTR	Exon 1 of 27	ENSP00000425320.2	P98194-8

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111823 AN: 152060 Hom.: 41510 Cov.: 33

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.732

GnomAD4 exome AF: 0.698 AC: 248021 AN: 355390 Hom.: 87269 Cov.: 5 AF XY: 0.697 AC XY: 128738 AN XY: 184732

African (AFR) AF: 0.844 AC: 7283 AN: 8630

American (AMR) AF: 0.734 AC: 7473 AN: 10176

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 8429 AN: 11350

East Asian (EAS) AF: 0.820 AC: 19922 AN: 24284

South Asian (SAS) AF: 0.690 AC: 15985 AN: 23154

European-Finnish (FIN) AF: 0.703 AC: 18426 AN: 26216

Middle Eastern (MID) AF: 0.749 AC: 2448 AN: 3268

European-Non Finnish (NFE) AF: 0.673 AC: 152740 AN: 226908

Other (OTH) AF: 0.716 AC: 15315 AN: 21404

GnomAD4 genome AF: 0.736 AC: 111938 AN: 152178 Hom.: 41568 Cov.: 33 AF XY: 0.739 AC XY: 54999 AN XY: 74396

African (AFR) AF: 0.840 AC: 34892 AN: 41522

American (AMR) AF: 0.733 AC: 11214 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2603 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4242 AN: 5172

South Asian (SAS) AF: 0.671 AC: 3240 AN: 4826

European-Finnish (FIN) AF: 0.717 AC: 7591 AN: 10584

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45782 AN: 67990

Other (OTH) AF: 0.729 AC: 1540 AN: 2112

Alfa AF: 0.714 Hom.: 10436

Bravo AF: 0.743

Asia WGS AF: 0.738 AC: 2565 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.50
PhyloP100		0.10
PromoterAI		0.0046	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1316658; hg19: chr3-130569557;