3-130850713-T-G

Position:

• chr3-130850713-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_001740492.2(LOC107986023):​n.1067-1714A>C variant causes a intron, non coding transcript 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: LOC107986023 XR_001740492.2 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105

Genes affected

LOC107986023 (HGNC:):

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107986023	XR_001740492.2	n.1067-1714A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000504381.5	c.-108T>G		5_prime_UTR_variant	1/27	2		ENSP00000425320
ATP2C1	ENST00000505330.5	c.-108T>G		5_prime_UTR_variant	1/27	2		ENSP00000423774
ATP2C1	ENST00000507488.6	c.-108T>G		5_prime_UTR_variant	1/28	2		ENSP00000421326

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

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.734

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.820

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.716

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

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.729

Alfa AF: 0.714 Hom.: 10436

Bravo AF: 0.743

Asia WGS AF: 0.738 AC: 2565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1316658; hg19: chr3-130569557;