NM_004612.4:c.-2C>T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_004612.4(TGFBR1):c.-2C>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 0.000262 in 1,082,854 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004612.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 211AN: 147236Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000759 AC: 71AN: 935516Hom.: 1 Cov.: 30 AF XY: 0.0000775 AC XY: 34AN XY: 438966
GnomAD4 genome AF: 0.00145 AC: 213AN: 147338Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 105AN XY: 71896
ClinVar
Submissions by phenotype
not specified Benign:2
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not provided Benign:2
Variant summary: This c.-2C>T variant substitutes a non-conserved nucleotide in the 5-prime untranslated region. The variant falls within the Kozak's sequence (gcc)gccRccAUGG; however, it does not involve the conserved nuncleotides in the sequence (AUGG and R are known to be highly conserved). This variant was found in 11/5008 chromosomes from Thousands Genomes Project at a frequency of 0.0021965, which is more than 1756 times greater than the maximal expected frequency of a pathogenic allele (0.0000013) in this gene (based on the disease prevalence of Aortopathy), suggesting this variant is benign. [The frequency data from NHLBI ESP and ExAC were not applicable either due to extremely low coverage or the nucleotide position not being covered.] The variant has not been reported in affected patients via literature. Two clinical labs (via ClinVar) have classified this variant as likely benign. Taken together, this variant as been classified as Benign. -
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Familial thoracic aortic aneurysm and aortic dissection Benign:1
This alteration is classified as 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. -
Multiple self-healing squamous epithelioma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at