Variant rs58202892 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_177438.3(DICER1):c.4206+11delG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3478 hom., cov: 0)

Exomes 𝑓: 0.13 ( 3819 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.185

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 -16 ACMG points.

BP6

Variant 14-95099768-AC-A is Benign according to our data. Variant chr14-95099768-AC-A is described in ClinVar as [Benign]. Clinvar id is 477182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95099768-AC-A is described in Lovd as [Likely_benign]. Variant chr14-95099768-AC-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 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+11delG		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+11delG		intron_variant		1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

29416

AN:

136650

Hom.:

3474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.0101

AC:

2092

AN:

207618

Hom.:

484

AF XY:

0.00921

AC XY:

1038

AN XY:

112732

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.00920

Gnomad ASJ exome

AF:

0.00661

Gnomad EAS exome

AF:

0.00658

Gnomad SAS exome

AF:

0.00896

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.00889

Gnomad OTH exome

AF:

0.00813

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.133

AC:

169683

AN:

1273308

Hom.:

3819

Cov.:

AF XY:

0.134

AC XY:

84536

AN XY:

631648

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.215

AC:

29450

AN:

136746

Hom.:

3478

Cov.:

AF XY:

0.216

AC XY:

14328

AN XY:

66340

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

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	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

DICER1-related tumor predisposition

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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