Variant 14-95099771-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_177438.3(DICER1):c.4206+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 240 hom., cov: 0)

Exomes 𝑓: 0.18 ( 1846 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.327

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]

DICER1 links:

DICER1 (HGNC:):

DICER1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-95099771-C-A is Benign according to our data. Variant chr14-95099771-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 315105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95099771-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3 linkuse as main transcript	c.4206+9G>T		intron_variant		ENST00000343455.8	NP_803187.1	Q9UPY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8 linkuse as main transcript	c.4206+9G>T		intron_variant		1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

7044

AN:

26688

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.286

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.467

AC:

79663

AN:

170614

Hom.:

29841

AF XY:

0.462

AC XY:

42700

AN XY:

92356

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.471

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.182

AC:

46963

AN:

257564

Hom.:

1846

Cov.:

AF XY:

0.193

AC XY:

24345

AN XY:

125984

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.264

AC:

7069

AN:

26768

Hom.:

240

Cov.:

AF XY:

0.276

AC XY:

3596

AN XY:

13006

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.838

Hom.:

4916

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 27, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

DICER1-related tumor predisposition

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This 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 submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Pleuropulmonary blastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Euthyroid goiter

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over