rs140143522

Variant names:

• chr16-28878386-CA-C
• rs140143522
• ENST00000691192.2:n.1550delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000691192.2(ATP2A1-AS1):​n.1550delT 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 0.34 (9453 hom., cov: 0)
  • Exomes 𝑓: 0.35 (20120 hom.)
• Consequence: ATP2A1-AS1 ENST00000691192.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 2 publications found

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]

ATP2A1 Gene-Disease associations (from GenCC):

• Brody myopathy

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-28878386-CA-C is Benign according to our data. Variant chr16-28878386-CA-C is described in ClinVar as [Benign]. Clinvar id is 1178419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A1	NM_004320.6	c.-285delA		upstream_gene_variant		ENST00000395503.9	NP_004311.1
ATP2A1	NM_173201.5	c.-285delA		upstream_gene_variant			NP_775293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A1-AS1	ENST00000691192.2	n.1550delT		non_coding_transcript_exon_variant	Exon 1 of 1
ATP2A1	ENST00000395503.9	c.-285delA		upstream_gene_variant		1	NM_004320.6	ENSP00000378879.5
ATP2A1	ENST00000357084.7	c.-285delA		upstream_gene_variant		2		ENSP00000349595.3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51639 AN: 151678 Hom.: 9424 Cov.: 0

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.345 AC: 107406 AN: 311030 Hom.: 20120 Cov.: 0 AF XY: 0.336 AC XY: 55591 AN XY: 165486

African (AFR) AF: 0.259 AC: 2344 AN: 9062

American (AMR) AF: 0.455 AC: 6494 AN: 14260

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 2479 AN: 9164

East Asian (EAS) AF: 0.124 AC: 2265 AN: 18236

South Asian (SAS) AF: 0.222 AC: 9230 AN: 41496

European-Finnish (FIN) AF: 0.418 AC: 7363 AN: 17594

Middle Eastern (MID) AF: 0.221 AC: 283 AN: 1282

European-Non Finnish (NFE) AF: 0.389 AC: 70903 AN: 182356

Other (OTH) AF: 0.344 AC: 6045 AN: 17580

GnomAD4 genome AF: 0.341 AC: 51733 AN: 151796 Hom.: 9453 Cov.: 0 AF XY: 0.339 AC XY: 25138 AN XY: 74186

African (AFR) AF: 0.265 AC: 10955 AN: 41384

American (AMR) AF: 0.406 AC: 6191 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3468

East Asian (EAS) AF: 0.120 AC: 618 AN: 5154

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4816

European-Finnish (FIN) AF: 0.421 AC: 4426 AN: 10524

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26631 AN: 67884

Other (OTH) AF: 0.308 AC: 650 AN: 2108

Alfa AF: 0.180 Hom.: 389

Bravo AF: 0.338

Asia WGS AF: 0.275 AC: 953 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs140143522; hg19: chr16-28889707; COSMIC: COSV59463027;