rs367764979

Variant names:

• chr14-95099768-ACAC-A
• rs367764979
• NM_177438.3:c.4206+9_4206+11delGTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_177438.3(DICER1):​c.4206+9_4206+11delGTG 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 0.47 (15172 hom., cov: 0)
  • Exomes 𝑓: 0.42 (21516 hom.)
  • Failed GnomAD Quality Control
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.410
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-95099768-ACAC-A is Benign according to our data. Variant chr14-95099768-ACAC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3	c.4206+9_4206+11delGTG		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	c.4206+9_4206+11delGTG		intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 64836 AN: 136574 Hom.: 15182 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.514

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.155 AC: 32212 AN: 207618 AF XY: 0.159

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.0965

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.150

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.417 AC: 509306 AN: 1220414 Hom.: 21516 AF XY: 0.417 AC XY: 252860 AN XY: 606122

African (AFR) AF: 0.285 AC: 7786 AN: 27326

American (AMR) AF: 0.405 AC: 14727 AN: 36390

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 8819 AN: 21364

East Asian (EAS) AF: 0.403 AC: 11290 AN: 28024

South Asian (SAS) AF: 0.410 AC: 28795 AN: 70260

European-Finnish (FIN) AF: 0.413 AC: 16842 AN: 40780

Middle Eastern (MID) AF: 0.400 AC: 1885 AN: 4714

European-Non Finnish (NFE) AF: 0.423 AC: 398351 AN: 941018

Other (OTH) AF: 0.412 AC: 20811 AN: 50538

GnomAD4 genome AF: 0.474 AC: 64839 AN: 136668 Hom.: 15172 Cov.: 0 AF XY: 0.473 AC XY: 31346 AN XY: 66296

African (AFR) AF: 0.274 AC: 9838 AN: 35906

American (AMR) AF: 0.497 AC: 6771 AN: 13614

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1715 AN: 3166

East Asian (EAS) AF: 0.504 AC: 2065 AN: 4098

South Asian (SAS) AF: 0.485 AC: 2052 AN: 4228

European-Finnish (FIN) AF: 0.497 AC: 4560 AN: 9182

Middle Eastern (MID) AF: 0.504 AC: 134 AN: 266

European-Non Finnish (NFE) AF: 0.571 AC: 36233 AN: 63432

Other (OTH) AF: 0.463 AC: 879 AN: 1900

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Nov 02, 2016

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: 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		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs367764979; hg19: chr14-95566105;