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
Consequence
NM_004612.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00180 AC: 269AN: 149324Hom.: 2 Cov.: 32
GnomAD4 exome AF: 0.000170 AC: 142AN: 836762Hom.: 1 Cov.: 13 AF XY: 0.000151 AC XY: 59AN XY: 389468
GnomAD4 genome AF: 0.00180 AC: 269AN: 149432Hom.: 2 Cov.: 32 AF XY: 0.00177 AC XY: 129AN XY: 73012
ClinVar
Submissions by phenotype
not specified Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at