rs199508452
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_177438.3(DICER1):c.4206+9_4206+15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,212,756 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0068 ( 10 hom., cov: 0)
Exomes 𝑓: 0.0047 ( 62 hom. )
Consequence
DICER1
NM_177438.3 intron
NM_177438.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.918
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 -16 ACMG points.
BP6
?
Variant 14-95099764-ACACACAC-A is Benign according to our data. Variant chr14-95099764-ACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00678 (812/119826) while in subpopulation AFR AF= 0.0195 (652/33446). AF 95% confidence interval is 0.0183. There are 10 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 812 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4206+9_4206+15del | intron_variant | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4206+9_4206+15del | intron_variant | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00676 AC: 810AN: 119750Hom.: 10 Cov.: 0
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GnomAD3 exomes AF: 0.00426 AC: 874AN: 205036Hom.: 154 AF XY: 0.00414 AC XY: 460AN XY: 111138
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GnomAD4 exome AF: 0.00471 AC: 5145AN: 1092930Hom.: 62 AF XY: 0.00487 AC XY: 2641AN XY: 541746
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GnomAD4 genome ? AF: 0.00678 AC: 812AN: 119826Hom.: 10 Cov.: 0 AF XY: 0.00631 AC XY: 364AN XY: 57720
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DICER1-related tumor predisposition Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Euthyroid goiter Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2019 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at