rs16952790
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005359.6(SMAD4):c.1308+1341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 152,288 control chromosomes in the GnomAD database, including 581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.047 ( 581 hom., cov: 32)
Consequence
SMAD4
NM_005359.6 intron
NM_005359.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.729
Genes affected
SMAD4 (HGNC:6770): (SMAD family member 4) This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasing blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [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=-0.88).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD4 | NM_005359.6 | c.1308+1341A>G | intron_variant | ENST00000342988.8 | |||
SMAD4 | NM_001407041.1 | c.1308+1341A>G | intron_variant | ||||
SMAD4 | NM_001407042.1 | c.1308+1341A>G | intron_variant | ||||
SMAD4 | NR_176265.1 | n.1846+1341A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD4 | ENST00000342988.8 | c.1308+1341A>G | intron_variant | 5 | NM_005359.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0465 AC: 7083AN: 152170Hom.: 577 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0467 AC: 7118AN: 152288Hom.: 581 Cov.: 32 AF XY: 0.0454 AC XY: 3382AN XY: 74476
GnomAD4 genome
?
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32
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3382
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74476
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62
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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