Variant rs748368348 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+9_4206+19delGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,580,912 control chromosomes in the GnomAD database, including 3,100 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 976 hom., cov: 0)

Exomes 𝑓: 0.090 ( 2124 hom. )

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 -16 ACMG points.

BP6

Variant 14-95099760-ACACACACACAC-A is Benign according to our data. Variant chr14-95099760-ACACACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95099760-ACACACACACAC-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3 link	c.4206+9_4206+19delGTGTGTGTGTG		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 link	c.4206+9_4206+19delGTGTGTGTGTG		intron_variant		1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.0922

AC:

13768

AN:

149290

Hom.:

974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0769

Gnomad NFE

AF:

0.0875

Gnomad OTH

AF:

0.0902

GnomAD3 exomes

AF:

0.0598

AC:

13933

AN:

233034

Hom.:

1725

AF XY:

0.0594

AC XY:

7539

AN XY:

126876

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.0679

Gnomad ASJ exome

AF:

0.0461

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.0678

Gnomad FIN exome

AF:

0.0553

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0905

AC:

129542

AN:

1431512

Hom.:

2124

AF XY:

0.0913

AC XY:

65000

AN XY:

711920

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.0871

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0890

Gnomad4 NFE exome

AF:

0.0797

Gnomad4 OTH exome

AF:

0.0938

GnomAD4 genome

AF:

0.0922

AC:

13770

AN:

149400

Hom.:

976

Cov.:

AF XY:

0.0985

AC XY:

7183

AN XY:

72954

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0875

Gnomad4 OTH

AF:

0.0893

Alfa

AF:

0.108

Hom.:

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

DICER1-related tumor predisposition

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2017

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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