9-99146570-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004612.4(TGFBR1):c.1216T>C(p.Leu406=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,614,018 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L406L) has been classified as Likely benign.
Frequency
Consequence
NM_004612.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR1 | NM_004612.4 | c.1216T>C | p.Leu406= | synonymous_variant | 7/9 | ENST00000374994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR1 | ENST00000374994.9 | c.1216T>C | p.Leu406= | synonymous_variant | 7/9 | 1 | NM_004612.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000295 AC: 74AN: 251216Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135758
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461704Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 727160
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74484
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 16, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 28, 2018 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 26, 2010 | This variant has not been previously reported in the literature nor been identif ied in our laboratory. It is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, nor predicted to alter splicing. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | - - |
Loeys-Dietz syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2018 | - - |
Multiple self-healing squamous epithelioma Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at