Variant rs199508452 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_177438.3(DICER1):c.4206+9_4206+15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,212,756 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 10 hom., cov: 0)

Exomes 𝑓: 0.0047 ( 62 hom. )

Consequence

DICER1
NM_177438.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-95099764-ACACACAC-A is Benign according to our data. Variant chr14-95099764-ACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00678 (812/119826) while in subpopulation AFR AF= 0.0195 (652/33446). AF 95% confidence interval is 0.0183. There are 10 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 812 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3 linkuse as main transcript	c.4206+9_4206+15del		intron_variant		ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8 linkuse as main transcript	c.4206+9_4206+15del		intron_variant		1	NM_177438.3	ENSP00000343745	P1	Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.00676

AC:

810

AN:

119750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00374

Gnomad ASJ

AF:

0.00109

Gnomad EAS

AF:

0.00720

Gnomad SAS

AF:

0.00505

Gnomad FIN

AF:

0.000244

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00784

GnomAD3 exomes

AF:

0.00426

AC:

874

AN:

205036

Hom.:

154

AF XY:

0.00414

AC XY:

460

AN XY:

111138

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.00445

Gnomad EAS exome

AF:

0.00378

Gnomad SAS exome

AF:

0.00456

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.00380

Gnomad OTH exome

AF:

0.00414

GnomAD4 exome

AF:

0.00471

AC:

5145

AN:

1092930

Hom.:

AF XY:

0.00487

AC XY:

2641

AN XY:

541746

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.00685

Gnomad4 ASJ exome

AF:

0.00500

Gnomad4 EAS exome

AF:

0.00982

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.00408

Gnomad4 NFE exome

AF:

0.00355

Gnomad4 OTH exome

AF:

0.00651

GnomAD4 genome

AF:

0.00678

AC:

812

AN:

119826

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

364

AN XY:

57720

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00109

Gnomad4 EAS

AF:

0.00725

Gnomad4 SAS

AF:

0.00506

Gnomad4 FIN

AF:

0.000244

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00774

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DICER1-related tumor predisposition

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Euthyroid goiter

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2019

- -

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