NM_145046.5:c.850G>A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_145046.5(CALR3):c.850G>A(p.Asp284Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,614,222 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_145046.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.850G>A | p.Asp284Asn | missense_variant | Exon 7 of 9 | ENST00000269881.8 | NP_659483.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.850G>A | p.Asp284Asn | missense_variant | Exon 7 of 9 | 1 | NM_145046.5 | ENSP00000269881.3 | ||
ENSG00000141979 | ENST00000409035.1 | n.*653G>A | non_coding_transcript_exon_variant | Exon 10 of 12 | 2 | ENSP00000386951.2 | ||||
ENSG00000141979 | ENST00000409035.1 | n.*653G>A | 3_prime_UTR_variant | Exon 10 of 12 | 2 | ENSP00000386951.2 | ||||
CALR3 | ENST00000602234.1 | n.524G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00438 AC: 666AN: 152218Hom.: 6 Cov.: 33
GnomAD3 exomes AF: 0.00140 AC: 353AN: 251494Hom.: 4 AF XY: 0.00118 AC XY: 160AN XY: 135920
GnomAD4 exome AF: 0.000510 AC: 746AN: 1461886Hom.: 4 Cov.: 46 AF XY: 0.000468 AC XY: 340AN XY: 727242
GnomAD4 genome AF: 0.00437 AC: 665AN: 152336Hom.: 6 Cov.: 33 AF XY: 0.00420 AC XY: 313AN XY: 74490
ClinVar
Submissions by phenotype
not provided Benign:4
Variant summary: The CALR3 c.850G>A (p.Asp284Asn) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 204/121410 control chromosomes (4 homozygotes) from ExAC, predominantly observed in the African subpopulation at a frequency of 0.017782 (185/10404). This frequency is about 711 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 African origin. In addition, multiple clinical diagnostic laboratories/reputable databases in ClinVar have classified this variant as benign. To our knowledge, this variant has not been reported in affected individuals in literature. Taken together, this variant is classified as benign. -
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Hypertrophic cardiomyopathy 19 Benign:3
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not specified Benign:2
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Hypertrophic cardiomyopathy;C0878544:Cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at