rs1555366154
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_177438.3(DICER1):c.5521C>T(p.Leu1841=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,858 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 (★★★). Synonymous variant affecting the same amino acid position (i.e. L1841L) has been classified as Likely benign.
Frequency
Consequence
NM_177438.3 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.5521C>T | p.Leu1841= | synonymous_variant | 25/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.5521C>T | p.Leu1841= | synonymous_variant | 25/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727236
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Benign:2
Likely benign, reviewed by expert panel | curation | ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen | May 18, 2022 | The NM_177438.2:c.5521C>T (p.Leu1841=) variant is a synonymous (silent) variant that is not predicted by MaxEntScan or SpliceAI to impact splicing (BP4, BP7). This variant is absent from gnomAD v2.1.1 and v.3.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely benign for DICER1 syndrome. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7, PM2_Supporting. (Bayesian Points: -1; VCEP specifications version 1; 02/11/22) - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2017 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at