rs1133170
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_000358.3(TGFBI):c.1416C>T(p.Leu472=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,600,388 control chromosomes in the GnomAD database, including 60,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6023 hom., cov: 33)
Exomes 𝑓: 0.27 ( 54617 hom. )
Consequence
TGFBI
NM_000358.3 synonymous
NM_000358.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.26
Genes affected
TGFBI (HGNC:11771): (transforming growth factor beta induced) This gene encodes an RGD-containing protein that binds to type I, II and IV collagens. The RGD motif is found in many extracellular matrix proteins modulating cell adhesion and serves as a ligand recognition sequence for several integrins. This protein plays a role in cell-collagen interactions and may be involved in endochondrial bone formation in cartilage. The protein is induced by transforming growth factor-beta and acts to inhibit cell adhesion. Mutations in this gene are associated with multiple types of corneal dystrophy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP7
?
Synonymous conserved (PhyloP=-1.26 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBI | NM_000358.3 | c.1416C>T | p.Leu472= | synonymous_variant | 11/17 | ENST00000442011.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBI | ENST00000442011.7 | c.1416C>T | p.Leu472= | synonymous_variant | 11/17 | 1 | NM_000358.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.279 AC: 42491AN: 152044Hom.: 6021 Cov.: 33
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GnomAD3 exomes AF: 0.269 AC: 66294AN: 246444Hom.: 9203 AF XY: 0.275 AC XY: 36706AN XY: 133592
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GnomAD4 exome AF: 0.273 AC: 394877AN: 1448226Hom.: 54617 Cov.: 33 AF XY: 0.275 AC XY: 197674AN XY: 717814
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GnomAD4 genome ? AF: 0.279 AC: 42524AN: 152162Hom.: 6023 Cov.: 33 AF XY: 0.280 AC XY: 20793AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Corneal dystrophy Benign:1
Benign, 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 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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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