rs17228212
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005902.4(SMAD3):c.533-478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 377,908 control chromosomes in the GnomAD database, including 12,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 3795 hom., cov: 33)
Exomes 𝑓: 0.26 ( 8692 hom. )
Consequence
SMAD3
NM_005902.4 intron
NM_005902.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0370
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 15-67166301-T-C is Benign according to our data. Variant chr15-67166301-T-C is described in ClinVar as [Benign]. Clinvar id is 1272319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.533-478T>C | intron_variant | ENST00000327367.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367.9 | c.533-478T>C | intron_variant | 1 | NM_005902.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.207 AC: 31468AN: 152068Hom.: 3795 Cov.: 33
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GnomAD4 exome AF: 0.259 AC: 58365AN: 225722Hom.: 8692 AF XY: 0.259 AC XY: 28573AN XY: 110334
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GnomAD4 genome ? AF: 0.207 AC: 31473AN: 152186Hom.: 3795 Cov.: 33 AF XY: 0.199 AC XY: 14786AN XY: 74384
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Coronary artery disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory | May 12, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at