rs772457274

chr14-95099762-ACACACACAC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_177438.3(DICER1):c.4206+9_4206+17del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,253,814 control chromosomes in the GnomAD database, including 102 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (52 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (50 hom.)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.918

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 14-95099762-ACACACACAC-A is Benign according to our data. Variant chr14-95099762-ACACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95099762-ACACACACAC-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2085/121112) while in subpopulation AFR AF= 0.0474 (1733/36580). AF 95% confidence interval is 0.0455. There are 52 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2079 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.4206+9_4206+17del		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.4206+9_4206+17del		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2079 AN: 121006 Hom.: 52 Cov.: 0

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00764

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.00513

Gnomad FIN AF: 0.00479

Gnomad MID AF: 0.0155

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00303 AC: 699 AN: 230604 Hom.: 56 AF XY: 0.00249 AC XY: 313 AN XY: 125578

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.000841

Gnomad EAS exome AF: 0.00196

Gnomad SAS exome AF: 0.00252

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00226

GnomAD4 exome AF: 0.00445 AC: 5039 AN: 1132702 Hom.: 50 AF XY: 0.00438 AC XY: 2460 AN XY: 561494

Gnomad4 AFR exome AF: 0.0479

Gnomad4 AMR exome AF: 0.00437

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.00515

Gnomad4 FIN exome AF: 0.00508

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00757

GnomAD4 genome AF: 0.0172 AC: 2085 AN: 121112 Hom.: 52 Cov.: 0 AF XY: 0.0172 AC XY: 1004 AN XY: 58326

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.00762

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0157

Gnomad4 SAS AF: 0.00513

Gnomad4 FIN AF: 0.00479

Gnomad4 NFE AF: 0.00283

Gnomad4 OTH AF: 0.0143

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Aug 03, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2019

See Variant Classification Assertion Criteria. -

DICER1-related tumor predisposition Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772457274; hg19: chr14-95566099;