rs9282871
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2
The NM_000660.7(TGFB1):c.-14G>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 0.00242 in 1,512,358 control chromosomes in the GnomAD database, including 79 homozygotes. 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 0.013 ( 41 hom., cov: 31)
Exomes 𝑓: 0.0013 ( 38 hom. )
Consequence
TGFB1
NM_000660.7 5_prime_UTR
NM_000660.7 5_prime_UTR
Scores
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.209
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]
TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1939/151248) while in subpopulation AFR AF= 0.0449 (1852/41262). AF 95% confidence interval is 0.0432. There are 41 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 41 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB1 | NM_000660.7 | c.-14G>A | 5_prime_UTR_variant | 1/7 | ENST00000221930.6 | ||
TGFB1 | XM_011527242.3 | c.-14G>A | 5_prime_UTR_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB1 | ENST00000221930.6 | c.-14G>A | 5_prime_UTR_variant | 1/7 | 1 | NM_000660.7 | P1 | ||
TMEM91 | ENST00000539627.5 | c.-30+1856C>T | intron_variant | 1 | |||||
TGFB1 | ENST00000600196.2 | upstream_gene_variant | 5 | ||||||
TGFB1 | ENST00000677934.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0128 AC: 1929AN: 151128Hom.: 41 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
1929
AN:
151128
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00295 AC: 337AN: 114120Hom.: 6 AF XY: 0.00240 AC XY: 149AN XY: 62176
GnomAD3 exomes
AF:
AC:
337
AN:
114120
Hom.:
AF XY:
AC XY:
149
AN XY:
62176
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00126 AC: 1717AN: 1361110Hom.: 38 Cov.: 33 AF XY: 0.00109 AC XY: 731AN XY: 669642
GnomAD4 exome
AF:
AC:
1717
AN:
1361110
Hom.:
Cov.:
33
AF XY:
AC XY:
731
AN XY:
669642
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0128 AC: 1939AN: 151248Hom.: 41 Cov.: 31 AF XY: 0.0123 AC XY: 906AN XY: 73926
GnomAD4 genome
?
AF:
AC:
1939
AN:
151248
Hom.:
Cov.:
31
AF XY:
AC XY:
906
AN XY:
73926
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
6
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at