rs3917200
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003239.5(TGFB3):c.755-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 1,613,214 control chromosomes in the GnomAD database, including 8,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.14 ( 2283 hom., cov: 32)
Exomes 𝑓: 0.084 ( 6336 hom. )
Consequence
TGFB3
NM_003239.5 intron
NM_003239.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.129
Genes affected
TGFB3 (HGNC:11769): (transforming growth factor beta 3) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]
IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 14-75963525-A-G is Benign according to our data. Variant chr14-75963525-A-G is described in ClinVar as [Benign]. Clinvar id is 674788.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-75963525-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB3 | NM_003239.5 | c.755-38T>C | intron_variant | ENST00000238682.8 | |||
TGFB3 | NM_001329938.2 | c.755-38T>C | intron_variant | ||||
TGFB3 | NM_001329939.2 | c.755-38T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB3 | ENST00000238682.8 | c.755-38T>C | intron_variant | 1 | NM_003239.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.137 AC: 20883AN: 152044Hom.: 2264 Cov.: 32
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GnomAD3 exomes AF: 0.0921 AC: 23034AN: 250042Hom.: 1538 AF XY: 0.0911 AC XY: 12312AN XY: 135210
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GnomAD4 exome AF: 0.0839 AC: 122611AN: 1461052Hom.: 6336 Cov.: 33 AF XY: 0.0844 AC XY: 61321AN XY: 726862
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GnomAD4 genome ? AF: 0.138 AC: 20945AN: 152162Hom.: 2283 Cov.: 32 AF XY: 0.134 AC XY: 9982AN XY: 74404
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
?
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