chr9-99105115-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_004612.4(TGFBR1):c.-91C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 986,194 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )
Consequence
TGFBR1
NM_004612.4 5_prime_UTR
NM_004612.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.107
Genes affected
TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 9-99105115-C-T is Benign according to our data. Variant chr9-99105115-C-T is described in ClinVar as [Benign]. Clinvar id is 2504011.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0018 (269/149432) while in subpopulation AFR AF= 0.00627 (257/40994). AF 95% confidence interval is 0.00564. There are 2 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 269 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR1 | NM_004612.4 | c.-91C>T | 5_prime_UTR_variant | 1/9 | ENST00000374994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR1 | ENST00000374994.9 | c.-91C>T | 5_prime_UTR_variant | 1/9 | 1 | NM_004612.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00180 AC: 269AN: 149324Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.000170 AC: 142AN: 836762Hom.: 1 Cov.: 13 AF XY: 0.000151 AC XY: 59AN XY: 389468
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GnomAD4 genome ? AF: 0.00180 AC: 269AN: 149432Hom.: 2 Cov.: 32 AF XY: 0.00177 AC XY: 129AN XY: 73012
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 03, 2023 | Variant summary: TGFBR1 c.-91C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.0019 in 28470 control chromosomes, predominantly at a frequency of 0.0063 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3360-fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFBR1 causing Loeys-Dietz Syndrome phenotype (1.9e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.-91C>T in individuals affected with Loeys-Dietz Syndrome or other TGFBR1-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
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