rs965942065
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_005359.6(SMAD4):āc.132A>Gā(p.Val44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,260 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V44V) has been classified as Likely benign.
Frequency
Consequence
NM_005359.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD4 | NM_005359.6 | c.132A>G | p.Val44= | synonymous_variant | 2/12 | ENST00000342988.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD4 | ENST00000342988.8 | c.132A>G | p.Val44= | synonymous_variant | 2/12 | 5 | NM_005359.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74396
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 30, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 30, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2021 | - - |
Hereditary cancer-predisposing syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 08, 2023 | - - |
Juvenile polyposis syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at