rs147388628
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004612.4(TGFBR1):āc.810T>Cā(p.Asn270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,614,008 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 (ā ā ).
Frequency
Genomes: š 0.00022 ( 0 hom., cov: 32)
Exomes š: 0.000049 ( 0 hom. )
Consequence
TGFBR1
NM_004612.4 synonymous
NM_004612.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.640
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 9-99142540-T-C is Benign according to our data. Variant chr9-99142540-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 415028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-99142540-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.64 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000223 (34/152302) while in subpopulation AFR AF= 0.00077 (32/41580). AF 95% confidence interval is 0.000559. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR1 | NM_004612.4 | c.810T>C | p.Asn270= | synonymous_variant | 5/9 | ENST00000374994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR1 | ENST00000374994.9 | c.810T>C | p.Asn270= | synonymous_variant | 5/9 | 1 | NM_004612.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251280Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135794
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GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727146
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74482
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 09, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2017 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 01, 2023 | - - |
TGFBR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 29, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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