2-188974389-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_000090.4(COL3A1):c.-101G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 835,122 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
COL3A1
NM_000090.4 5_prime_UTR
NM_000090.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.31
Genes affected
COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000789 (12/152000) while in subpopulation AMR AF= 0.00072 (11/15268). AF 95% confidence interval is 0.000403. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.-101G>A | 5_prime_UTR_variant | 1/51 | ENST00000304636.9 | ||
LOC105373791 | XR_007087614.1 | n.110-3910C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.-101G>A | 5_prime_UTR_variant | 1/51 | 1 | NM_000090.4 | P1 | ||
COL3A1 | ENST00000450867.2 | c.-101G>A | 5_prime_UTR_variant | 1/50 | 1 | ||||
COL3A1 | ENST00000470167.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152000Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.000130 AC: 89AN: 683122Hom.: 0 Cov.: 9 AF XY: 0.0000979 AC XY: 35AN XY: 357414
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at