chr18-48950170-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_005904.4(SMAD7):c.255C>T(p.Ala85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000404 in 1,485,298 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
SMAD7
NM_005904.4 synonymous
NM_005904.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.45
Genes affected
SMAD7 (HGNC:6773): (SMAD family member 7) The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 18-48950170-G-A is Benign according to our data. Variant chr18-48950170-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034497.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.45 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD7 | NM_005904.4 | c.255C>T | p.Ala85= | synonymous_variant | 1/4 | ENST00000262158.8 | |
SMAD7 | NM_001190821.2 | c.255C>T | p.Ala85= | synonymous_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD7 | ENST00000262158.8 | c.255C>T | p.Ala85= | synonymous_variant | 1/4 | 1 | NM_005904.4 | P4 | |
SMAD7 | ENST00000589634.1 | c.255C>T | p.Ala85= | synonymous_variant | 1/4 | 4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151910Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000150 AC: 2AN: 1333388Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1AN XY: 657278
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151910Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74224
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SMAD7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at