15-67066040-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_005902.4(SMAD3):c.-115C>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 0.0000439 in 546,998 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 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
SMAD3
NM_005902.4 5_prime_UTR
NM_005902.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.64
Genes affected
SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 15-67066040-C-T is Benign according to our data. Variant chr15-67066040-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 316858.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000113 (17/150578) while in subpopulation EAS AF= 0.00299 (15/5024). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.-115C>T | 5_prime_UTR_variant | 1/9 | ENST00000327367.9 | ||
SMAD3 | NM_001407011.1 | c.-115C>T | 5_prime_UTR_variant | 1/10 | |||
SMAD3 | NM_001407012.1 | c.-115C>T | 5_prime_UTR_variant | 1/8 | |||
SMAD3 | NM_001407013.1 | c.-115C>T | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367.9 | c.-115C>T | 5_prime_UTR_variant | 1/9 | 1 | NM_005902.4 | P1 | ||
SMAD3 | ENST00000560424.2 | c.-115C>T | 5_prime_UTR_variant | 1/10 | 3 | ||||
SMAD3 | ENST00000559460.6 | c.-110+2096C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000113 AC: 17AN: 150468Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000177 AC: 7AN: 396420Hom.: 0 Cov.: 6 AF XY: 0.0000147 AC XY: 3AN XY: 204344
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GnomAD4 genome AF: 0.000113 AC: 17AN: 150578Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 9AN XY: 73600
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Loeys-Dietz syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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