9-99105217-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_004612.4(TGFBR1):c.12G>A(p.Ala4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,080,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
TGFBR1
NM_004612.4 synonymous
NM_004612.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.35
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 9-99105217-G-A is Benign according to our data. Variant chr9-99105217-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1177254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.35 with no splicing effect.
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFBR1 | NM_004612.4 | c.12G>A | p.Ala4= | synonymous_variant | 1/9 | ENST00000374994.9 | NP_004603.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFBR1 | ENST00000374994.9 | c.12G>A | p.Ala4= | synonymous_variant | 1/9 | 1 | NM_004612.4 | ENSP00000364133 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000135 AC: 2AN: 147634Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000750 AC: 7AN: 933264Hom.: 0 Cov.: 30 AF XY: 0.00000913 AC XY: 4AN XY: 438244
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GnomAD4 genome AF: 0.0000135 AC: 2AN: 147634Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1AN XY: 71944
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 03, 2021 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 04, 2023 | - - |
Computational scores
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Benign
CADD
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at