rs763704682

Variant names:

Your query was ambiguous. Multiple possible variants found:

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+8_4206+9insTTGT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 26,826 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 52 hom., cov: 30)

Exomes 𝑓: 0.0045 ( 44 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.425

Publications

2 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 14-95099771-C-CACAA is Benign according to our data. Variant chr14-95099771-C-CACAA is described in ClinVar as Benign. ClinVar VariationId is 221051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3 link	c.4206+8_4206+9insTTGT		splice_region_variant, intron_variant	Intron 22 of 26	ENST00000343455.8	NP_803187.1	Q9UPY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8 link	c.4206+8_4206+9insTTGT		splice_region_variant, intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.0528

AC:

1413

AN:

26746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0611

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00296

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.0607

GnomAD2 exomes

AF:

0.00329

AC:

561

AN:

170614

AF XY:

0.00241

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000713

Gnomad EAS exome

AF:

0.0000787

Gnomad FIN exome

AF:

0.0000797

Gnomad NFE exome

AF:

0.000463

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00449

AC:

1231

AN:

274410

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

581

AN XY:

134510

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0589

AC:

750

AN:

12742

American (AMR)

AF:

0.0185

AC:

AN:

4964

Ashkenazi Jewish (ASJ)

AF:

0.000654

AC:

AN:

4586

East Asian (EAS)

AF:

0.000413

AC:

AN:

2420

South Asian (SAS)

AF:

0.00310

AC:

AN:

14506

European-Finnish (FIN)

AF:

0.000554

AC:

AN:

9026

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

1586

European-Non Finnish (NFE)

AF:

0.000935

AC:

199

AN:

212896

Other (OTH)

AF:

0.0107

AC:

125

AN:

11684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.0528

AC:

1416

AN:

26826

Hom.:

Cov.:

AF XY:

0.0491

AC XY:

640

AN XY:

13032

show subpopulations

African (AFR)

AF:

0.0895

AC:

1237

AN:

13820

American (AMR)

AF:

0.0612

AC:

128

AN:

2092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

536

East Asian (EAS)

AF:

0.00

AC:

AN:

194

South Asian (SAS)

AF:

0.00292

AC:

AN:

684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00339

AC:

AN:

7088

Other (OTH)

AF:

0.0595

AC:

AN:

420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

DICER1-related tumor predisposition

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.42

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