19-18788580-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000095.3(COMP):c.762+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,556,756 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000095.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COMP | ENST00000222271.7 | c.762+12C>A | intron_variant | Intron 7 of 18 | 1 | NM_000095.3 | ENSP00000222271.2 | |||
COMP | ENST00000542601.6 | c.663+12C>A | intron_variant | Intron 6 of 17 | 1 | ENSP00000439156.2 | ||||
COMP | ENST00000425807.1 | c.603+12C>A | intron_variant | Intron 6 of 17 | 2 | ENSP00000403792.1 |
Frequencies
GnomAD3 genomes AF: 0.00430 AC: 655AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000991 AC: 153AN: 154426Hom.: 0 AF XY: 0.000855 AC XY: 71AN XY: 83060
GnomAD4 exome AF: 0.000470 AC: 660AN: 1404444Hom.: 3 Cov.: 36 AF XY: 0.000427 AC XY: 296AN XY: 693526
GnomAD4 genome AF: 0.00431 AC: 656AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.00438 AC XY: 326AN XY: 74476
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:1
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Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Multiple epiphyseal dysplasia type 1 Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at