rs1989457
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000660.7(TGFB1):c.517-1346A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Consequence
TGFB1
NM_000660.7 intron
NM_000660.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.02
Genes affected
TGFB1 (HGNC:11766): (transforming growth factor beta 1) 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 TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB1 | NM_000660.7 | c.517-1346A>T | intron_variant | ENST00000221930.6 | |||
TGFB1 | XM_011527242.3 | c.517-1346A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB1 | ENST00000221930.6 | c.517-1346A>T | intron_variant | 1 | NM_000660.7 | P1 | |||
TGFB1 | ENST00000597453.1 | n.48-1346A>T | intron_variant, non_coding_transcript_variant | 1 | |||||
TGFB1 | ENST00000600196.2 | c.517-1346A>T | intron_variant | 5 | |||||
TGFB1 | ENST00000677934.1 | c.517-1346A>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151832Hom.: 0 Cov.: 31
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151832Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74120
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ClinVar
Not reported inComputational 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