Variant rs745445238 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_177438.3(DICER1):c.4206+9_4206+13del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 26 hom., cov: 0)

Exomes 𝑓: 0.12 ( 776 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.918

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP6

Variant 14-95099766-ACACAC-A is Benign according to our data. Variant chr14-95099766-ACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 429146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3 linkuse as main transcript	c.4206+9_4206+13del		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8 linkuse as main transcript	c.4206+9_4206+13del		intron_variant		1	NM_177438.3	P1	Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1876

AN:

130922

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.0181

Gnomad AMR

AF:

0.00951

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0105

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.0132

GnomAD3 exomes

AF:

0.0351

AC:

7362

AN:

209476

Hom.:

1719

AF XY:

0.0360

AC XY:

4096

AN XY:

113754

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0418

Gnomad EAS exome

AF:

0.0239

Gnomad SAS exome

AF:

0.0360

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.123

AC:

147255

AN:

1194126

Hom.:

776

AF XY:

0.125

AC XY:

73949

AN XY:

593282

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0143

AC:

1877

AN:

131010

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

943

AN XY:

63440

show subpopulations

Gnomad4 AFR

AF:

0.0330

Gnomad4 AMR

AF:

0.00949

Gnomad4 ASJ

AF:

0.0103

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0304

Gnomad4 FIN

AF:

0.0110

Gnomad4 NFE

AF:

0.00492

Gnomad4 OTH

AF:

0.0131

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2019

See Variant Classification Assertion Criteria. -

DICER1-related tumor predisposition

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2016

This alteration is classified as likely benign based on a combination of the following: 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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