Variant rs746597527 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+21delGTGTGTGTGTGTG 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 0.0019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0048 ( 35 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:3

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:

DICER1 (HGNC:):

DICER1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-95099758-ACACACACACACAC-A is Benign according to our data. Variant chr14-95099758-ACACACACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477188.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 = 0.00185 (278/149996) while in subpopulation AFR AF= 0.00458 (182/39724). AF 95% confidence interval is 0.00404. There are 0 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 278 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+21delGTGTGTGTGTGTG		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+9_4206+21delGTGTGTGTGTGTG		intron_variant		1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

277

AN:

149888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00271

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00352

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.00290

GnomAD3 exomes

AF:

0.00819

AC:

1905

AN:

232686

Hom.:

137

AF XY:

0.00835

AC XY:

1059

AN XY:

126816

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.00938

Gnomad ASJ exome

AF:

0.00609

Gnomad EAS exome

AF:

0.0297

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.00738

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00672

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00483

AC:

6974

AN:

1443068

Hom.:

AF XY:

0.00510

AC XY:

3660

AN XY:

718046

show subpopulations

Gnomad4 AFR exome

AF:

0.00466

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.00416

Gnomad4 EAS exome

AF:

0.0536

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00792

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.00185

AC:

278

AN:

149996

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

144

AN XY:

73270

show subpopulations

Gnomad4 AFR

AF:

0.00458

Gnomad4 AMR

AF:

0.00132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00272

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.00352

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.00288

Alfa

AF:

0.00174

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely 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 15, 2019

- -

DICER1-related tumor predisposition

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

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