rs143158265
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_145046.5(CALR3):c.483C>A(p.Ile161Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,596,318 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_145046.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.483C>A | p.Ile161Ile | synonymous_variant | Exon 4 of 9 | ENST00000269881.8 | NP_659483.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.483C>A | p.Ile161Ile | synonymous_variant | Exon 4 of 9 | 1 | NM_145046.5 | ENSP00000269881.3 | ||
ENSG00000141979 | ENST00000409035.1 | n.*482-2387C>A | intron_variant | Intron 8 of 11 | 2 | ENSP00000386951.2 | ||||
CALR3 | ENST00000600762.1 | c.267C>A | p.Ile89Ile | synonymous_variant | Exon 3 of 4 | 3 | ENSP00000471533.1 |
Frequencies
GnomAD3 genomes AF: 0.00176 AC: 268AN: 152110Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00211 AC: 529AN: 250414Hom.: 2 AF XY: 0.00199 AC XY: 269AN XY: 135352
GnomAD4 exome AF: 0.00105 AC: 1516AN: 1444090Hom.: 10 Cov.: 28 AF XY: 0.00107 AC XY: 769AN XY: 719598
GnomAD4 genome AF: 0.00176 AC: 268AN: 152228Hom.: 2 Cov.: 32 AF XY: 0.00238 AC XY: 177AN XY: 74430
ClinVar
Submissions by phenotype
not specified Benign:3
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Hypertrophic cardiomyopathy 19 Benign:2
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CALR3-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Variant summary: The CALR3 c.483C>A (p.Ile161Ile) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SF2/ASF. However, these predictions have yet to be confirmed by functional studies. This variant was found in 209/112688 control chromosomes (1 homozygote) from ExAC, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.01888 (122/6462). This frequency is about 755 times the estimated maximal expected allele frequency of a pathogenic CALR3 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. One clinical diagnostic laboratory has classified this variant as benign. To our knowledge, the variant has not been reported in affected individuals in literature. Taken together, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at