chr16-28878660-G-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1
The NM_004320.6(ATP2A1):c.-12G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000113 in 1,588,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
ATP2A1
NM_004320.6 5_prime_UTR
NM_004320.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.26
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 16-28878660-G-A is Benign according to our data. Variant chr16-28878660-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 384851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000164 (25/152314) while in subpopulation EAS AF= 0.00483 (25/5172). AF 95% confidence interval is 0.00336. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.-12G>A | 5_prime_UTR_variant | 1/23 | ENST00000395503.9 | ||
ATP2A1 | NM_173201.5 | c.-12G>A | 5_prime_UTR_variant | 1/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.-12G>A | 5_prime_UTR_variant | 1/23 | 1 | NM_004320.6 | P4 | ||
ATP2A1-AS1 | ENST00000691192.2 | n.1277C>T | non_coding_transcript_exon_variant | 1/1 | |||||
ATP2A1 | ENST00000357084.7 | c.-12G>A | 5_prime_UTR_variant | 1/22 | 2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000407 AC: 86AN: 211246Hom.: 0 AF XY: 0.000361 AC XY: 41AN XY: 113662
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GnomAD4 exome AF: 0.000108 AC: 155AN: 1435862Hom.: 0 Cov.: 30 AF XY: 0.0000899 AC XY: 64AN XY: 712168
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2016 | 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. - |
Brody myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at