18-51067085-T-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005359.6(SMAD4):āc.1206T>Cā(p.Leu402=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,382 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L402L) has been classified as Likely benign.
Frequency
Consequence
NM_005359.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD4 | NM_005359.6 | c.1206T>C | p.Leu402= | synonymous_variant | 10/12 | ENST00000342988.8 | |
SMAD4 | NM_001407041.1 | c.1206T>C | p.Leu402= | synonymous_variant | 10/12 | ||
SMAD4 | NM_001407042.1 | c.1206T>C | p.Leu402= | synonymous_variant | 10/12 | ||
SMAD4 | NR_176265.1 | n.1744T>C | non_coding_transcript_exon_variant | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD4 | ENST00000342988.8 | c.1206T>C | p.Leu402= | synonymous_variant | 10/12 | 5 | NM_005359.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460382Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726600
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 28, 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 syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at