14-95095812-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_177438.3(DICER1):​c.5095+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,750 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00064 ( 7 hom. )

Consequence

DICER1
NM_177438.3 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.174
Variant links:
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 14-95095812-G-A is Benign according to our data. Variant chr14-95095812-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 135513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95095812-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00536 (816/152290) while in subpopulation AFR AF= 0.018 (749/41556). AF 95% confidence interval is 0.017. There are 3 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 816 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DICER1NM_177438.3 linkuse as main transcriptc.5095+13C>T intron_variant ENST00000343455.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DICER1ENST00000343455.8 linkuse as main transcriptc.5095+13C>T intron_variant 1 NM_177438.3 P1Q9UPY3-1

Frequencies

GnomAD3 genomes
AF:
0.00534
AC:
812
AN:
152172
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.000963
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00527
GnomAD3 exomes
AF:
0.00140
AC:
350
AN:
250766
Hom.:
3
AF XY:
0.00105
AC XY:
143
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.0167
Gnomad AMR exome
AF:
0.00104
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.000871
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000981
GnomAD4 exome
AF:
0.000640
AC:
935
AN:
1461460
Hom.:
7
Cov.:
31
AF XY:
0.000569
AC XY:
414
AN XY:
727042
show subpopulations
Gnomad4 AFR exome
AF:
0.0182
Gnomad4 AMR exome
AF:
0.00145
Gnomad4 ASJ exome
AF:
0.000880
Gnomad4 EAS exome
AF:
0.000529
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000105
Gnomad4 OTH exome
AF:
0.00152
GnomAD4 genome
AF:
0.00536
AC:
816
AN:
152290
Hom.:
3
Cov.:
33
AF XY:
0.00508
AC XY:
378
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0180
Gnomad4 AMR
AF:
0.00274
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00522
Alfa
AF:
0.00237
Hom.:
0
Bravo
AF:
0.00612
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 14, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 27, 2015- -
Benign, criteria provided, single submitterclinical testingCenter for Genomic Medicine, Rigshospitalet, Copenhagen University HospitalAug 15, 2023- -
DICER1-related tumor predisposition Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Pleuropulmonary blastoma Benign:1
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 14, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.0
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs116247322; hg19: chr14-95562149; COSMIC: COSV58616024; COSMIC: COSV58616024; API