rs368741914
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_177438.3(DICER1):c.366G>A(p.Gly122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,612,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 1 hom. )
Consequence
DICER1
NM_177438.3 synonymous
NM_177438.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
Variant 14-95131581-C-T is Benign according to our data. Variant chr14-95131581-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 220875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.08 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000158 (24/152090) while in subpopulation NFE AF= 0.000309 (21/68008). AF 95% confidence interval is 0.000207. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.366G>A | p.Gly122= | synonymous_variant | 4/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.366G>A | p.Gly122= | synonymous_variant | 4/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 251434Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135892
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GnomAD4 exome AF: 0.000332 AC: 485AN: 1460366Hom.: 1 Cov.: 30 AF XY: 0.000330 AC XY: 240AN XY: 726618
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74288
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 24, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2020 | - - |
DICER1-related tumor predisposition Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at