16-28878376-C-CT

Position:

• chr16-28878376-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000691192.2(ATP2A1-AS1):​n.1560_1561insA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7930 hom., cov: 20)
  • Exomes 𝑓: 0.33 (17226 hom.)
• Consequence: ATP2A1-AS1 ENST00000691192.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42

Genes affected

ATP2A1-AS1 (HGNC:51370): (ATP2A1 antisense RNA 1)

ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-28878376-C-CT is Benign according to our data. Variant chr16-28878376-C-CT is described in ClinVar as [Benign]. Clinvar id is 1291696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A1-AS1	ENST00000691192.2	n.1560_1561insA		non_coding_transcript_exon_variant	1/1
ATP2A1	ENST00000357084.7			upstream_gene_variant		2		ENSP00000349595	A1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43115 AN: 149682 Hom.: 7918 Cov.: 20

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.330 AC: 92424 AN: 280324 Hom.: 17226 Cov.: 0 AF XY: 0.320 AC XY: 47930 AN XY: 149758

Gnomad4 AFR exome AF: 0.0634

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.288 AC: 43136 AN: 149768 Hom.: 7930 Cov.: 20 AF XY: 0.287 AC XY: 21027 AN XY: 73230

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.272

Alfa AF: 0.334 Hom.: 1027

Asia WGS AF: 0.214 AC: 736 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201017113; hg19: chr16-28889697;