rs8055138

Variant names:

• chr16-28880144-C-T
• rs8055138
• NM_004320.6:c.219+561C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004320.6(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 NM_004320.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• Publications: 28 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004320.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A1	NM_004320.6	MANE Select	c.219+561C>T		intron	N/A	NP_004311.1	O14983-2
	ATP2A1	NM_173201.5		c.219+561C>T		intron	N/A	NP_775293.1	O14983-1
	ATP2A1	NM_001286075.2		c.-157+50C>T		intron	N/A	NP_001273004.1	O14983-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A1	ENST00000395503.9	TSL:1 MANE Select	c.219+561C>T		intron	N/A	ENSP00000378879.5	O14983-2
	ATP2A1	ENST00000971328.1		c.219+561C>T		intron	N/A	ENSP00000641387.1
	ATP2A1	ENST00000357084.7	TSL:2	c.219+561C>T		intron	N/A	ENSP00000349595.3	O14983-1

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

African (AFR) AF: 0.246 AC: 3890 AN: 15830

American (AMR) AF: 0.449 AC: 731 AN: 1628

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 1350 AN: 5254

East Asian (EAS) AF: 0.104 AC: 387 AN: 3726

South Asian (SAS) AF: 0.220 AC: 3730 AN: 16980

European-Finnish (FIN) AF: 0.405 AC: 196 AN: 484

Middle Eastern (MID) AF: 0.235 AC: 391 AN: 1662

European-Non Finnish (NFE) AF: 0.400 AC: 307942 AN: 769202

Other (OTH) AF: 0.346 AC: 9633 AN: 27830

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

African (AFR) AF: 0.265 AC: 11007 AN: 41536

American (AMR) AF: 0.405 AC: 6195 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3470

East Asian (EAS) AF: 0.120 AC: 622 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4828

European-Finnish (FIN) AF: 0.422 AC: 4459 AN: 10566

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

European-Non Finnish (NFE) AF: 0.392 AC: 26660 AN: 67930

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.374 Hom.: 2019

Bravo AF: 0.339

Asia WGS AF: 0.274 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		0.50
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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