rs201415999
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BS2BP4BP7
This summary comes from the ClinGen Evidence Repository: The NM_177438.2:c.4647C>T (p.His1549=) variant is a synonymous (silent) variant that is not predicted by MaxEntScan or SpliceAI to impact splicing (BP4, BP7). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (SCV000661822.3, SCV000563438.6) (BS2). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP7, BP4, BS2. (Bayesian Points: -6; VCEP specifications version 1; 02/11/2022) LINK:https://erepo.genome.network/evrepo/ui/classification/CA7330821/MONDO:0017288/024
Frequency
Consequence
NM_177438.3 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4647C>T | p.His1549= | synonymous_variant | 23/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4647C>T | p.His1549= | synonymous_variant | 23/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251448Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135894
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000127 AC XY: 92AN XY: 727248
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74376
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.4647C>T (p.His1549=) variant is a synonymous (silent) variant that is not predicted by MaxEntScan or SpliceAI to impact splicing (BP4, BP7). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (SCV000661822.3, SCV000563438.6) (BS2). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP7, BP4, BS2. (Bayesian Points: -6; VCEP specifications version 1; 02/11/2022) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 21, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at