chr4-145542814-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005900.3(SMAD1):c.775+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 645,584 control chromosomes in the GnomAD database, including 98,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.58 ( 26284 hom., cov: 32)
Exomes 𝑓: 0.53 ( 72510 hom. )
Consequence
SMAD1
NM_005900.3 intron
NM_005900.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.176
Genes affected
SMAD1 (HGNC:6767): (SMAD family member 1) The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 4-145542814-T-C is Benign according to our data. Variant chr4-145542814-T-C is described in ClinVar as [Benign]. Clinvar id is 1249634.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD1 | NM_005900.3 | c.775+116T>C | intron_variant | ENST00000302085.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD1 | ENST00000302085.9 | c.775+116T>C | intron_variant | 1 | NM_005900.3 | P1 | |||
SMAD1 | ENST00000394092.6 | c.775+116T>C | intron_variant | 1 | P1 | ||||
SMAD1 | ENST00000515385.1 | c.775+116T>C | intron_variant | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.578 AC: 87811AN: 151908Hom.: 26238 Cov.: 32
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GnomAD4 exome AF: 0.531 AC: 262205AN: 493558Hom.: 72510 AF XY: 0.533 AC XY: 139576AN XY: 261742
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GnomAD4 genome ? AF: 0.578 AC: 87913AN: 152026Hom.: 26284 Cov.: 32 AF XY: 0.574 AC XY: 42615AN XY: 74298
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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