16-28878165-C-A

Variant names:

• chr16-28878165-C-A
• rs3888190
• ENST00000691192.2:n.1772G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000691192.2(ATP2A1-AS1):​n.1772G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 150,134 control chromosomes in the GnomAD database, including 9,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9471 hom., cov: 28)
• Consequence: ATP2A1-AS1 ENST00000691192.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 115 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-28878165-C-A is Benign according to our data. Variant chr16-28878165-C-A is described in ClinVar as [Benign]. Clinvar id is 671198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A1-AS1	ENST00000691192.2	n.1772G>T		non_coding_transcript_exon_variant	Exon 1 of 1
ATP2A1	ENST00000357084.7	c.-507C>A		upstream_gene_variant		2		ENSP00000349595.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51466 AN: 150016 Hom.: 9442 Cov.: 28

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 51560 AN: 150134 Hom.: 9471 Cov.: 28 AF XY: 0.342 AC XY: 25026 AN XY: 73188

African (AFR) AF: 0.267 AC: 10878 AN: 40682

American (AMR) AF: 0.408 AC: 6167 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 929 AN: 3452

East Asian (EAS) AF: 0.120 AC: 602 AN: 5030

South Asian (SAS) AF: 0.220 AC: 1042 AN: 4740

European-Finnish (FIN) AF: 0.428 AC: 4407 AN: 10302

Middle Eastern (MID) AF: 0.229 AC: 66 AN: 288

European-Non Finnish (NFE) AF: 0.394 AC: 26601 AN: 67542

Other (OTH) AF: 0.311 AC: 648 AN: 2082

Alfa AF: 0.369 Hom.: 25705

Bravo AF: 0.339

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.54
PhyloP100		-1.5
PromoterAI		0.0078	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3888190; hg19: chr16-28889486;