12-47973403-G-A
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_001844.5(COL2A1):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,614,058 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001844.5 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518 | c.*4C>T | 3_prime_UTR_variant | Exon 54 of 54 | 1 | NM_001844.5 | ENSP00000369889.3 | |||
COL2A1 | ENST00000493991.5 | n.3554C>T | non_coding_transcript_exon_variant | Exon 37 of 37 | 2 | |||||
COL2A1 | ENST00000337299.7 | c.*4C>T | downstream_gene_variant | 1 | ENSP00000338213.6 |
Frequencies
GnomAD3 genomes AF: 0.0213 AC: 3233AN: 152050Hom.: 90 Cov.: 32
GnomAD3 exomes AF: 0.00967 AC: 2431AN: 251494Hom.: 52 AF XY: 0.00840 AC XY: 1142AN XY: 135922
GnomAD4 exome AF: 0.00608 AC: 8891AN: 1461890Hom.: 122 Cov.: 31 AF XY: 0.00580 AC XY: 4220AN XY: 727244
GnomAD4 genome AF: 0.0213 AC: 3245AN: 152168Hom.: 91 Cov.: 32 AF XY: 0.0212 AC XY: 1581AN XY: 74408
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:1
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. -
Stickler syndrome 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. -
Type II Collagenopathies 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. -
Connective tissue disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at