rs748368348

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

DICER1-related tumor predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
pleuropulmonary blastoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
DICER1 syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DICER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 477187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DICER1	NM_177438.3 link	c.4206+9_4206+19delGTGTGTGTGTG		intron_variant	Intron 22 of 26	ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8 link	c.4206+9_4206+19delGTGTGTGTGTG		intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3

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

GnomAD2 exomes

AF:

0.0598

AC:

13933

AN:

233034

AF XY:

0.0594

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 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

African (AFR)

AF:

0.0305

AC:

963

AN:

31622

American (AMR)

AF:

0.129

AC:

5587

AN:

43358

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

2234

AN:

25650

East Asian (EAS)

AF:

0.330

AC:

12676

AN:

38384

South Asian (SAS)

AF:

0.125

AC:

10445

AN:

83820

European-Finnish (FIN)

AF:

0.0890

AC:

4376

AN:

49170

Middle Eastern (MID)

AF:

0.0920

AC:

519

AN:

5644

European-Non Finnish (NFE)

AF:

0.0797

AC:

87192

AN:

1094676

Other (OTH)

AF:

0.0938

AC:

5550

AN:

59188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

4835

9670

14505

19340

24175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3630

7260

10890

14520

18150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0922

AC:

13770

AN:

149400

Hom.:

976

Cov.:

AF XY:

0.0985

AC XY:

7183

AN XY:

72954

show subpopulations

African (AFR)

AF:

0.0363

AC:

1430

AN:

39420

American (AMR)

AF:

0.144

AC:

2178

AN:

15110

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3454

East Asian (EAS)

AF:

0.369

AC:

1890

AN:

5122

South Asian (SAS)

AF:

0.139

AC:

664

AN:

4778

European-Finnish (FIN)

AF:

0.104

AC:

1082

AN:

10430

Middle Eastern (MID)

AF:

0.0793

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0875

AC:

5931

AN:

67800

Other (OTH)

AF:

0.0893

AC:

186

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

548

1097

1645

2194

2742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 15, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DICER1-related tumor predisposition

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Sep 28, 2017

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

PhyloP100

0.92

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over