rs8055138

Positions:

• chr16-28880144-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395503.9(ATP2A1):​c.219+561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 994,692 control chromosomes in the GnomAD database, including 74,422 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9510 hom., cov: 32)
  • Exomes 𝑓: 0.39 (64912 hom.)
• Consequence: ATP2A1 ENST00000395503.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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/exons	MANE	Protein	UniProt
ATP2A1	NM_004320.6	c.219+561C>T		intron_variant		ENST00000395503.9	NP_004311.1
ATP2A1	NM_001286075.2	c.-157+50C>T		intron_variant			NP_001273004.1
ATP2A1	NM_173201.5	c.219+561C>T		intron_variant			NP_775293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A1	ENST00000395503.9	c.219+561C>T		intron_variant		1	NM_004320.6	ENSP00000378879	P4

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51765 AN: 151978 Hom.: 9481 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.390 AC: 328250 AN: 842596 Hom.: 64912 Cov.: 28 AF XY: 0.390 AC XY: 152015 AN XY: 389554

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.341 AC: 51858 AN: 152096 Hom.: 9510 Cov.: 32 AF XY: 0.339 AC XY: 25230 AN XY: 74356

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.310

Alfa AF: 0.377 Hom.: 1996

Bravo AF: 0.339

Asia WGS AF: 0.274 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8055138; hg19: chr16-28891465; COSMIC: COSV63922264; COSMIC: COSV63922264;