rs199508452

chr14-95099764-ACACACAC-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+15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,212,756 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (10 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (62 hom.)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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 14-95099764-ACACACAC-A is Benign according to our data. Variant chr14-95099764-ACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477185.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 = 0.00678 (812/119826) while in subpopulation AFR AF= 0.0195 (652/33446). AF 95% confidence interval is 0.0183. There are 10 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 810 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.4206+9_4206+15del		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.4206+9_4206+15del		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 810 AN: 119750 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00109

Gnomad EAS AF: 0.00720

Gnomad SAS AF: 0.00505

Gnomad FIN AF: 0.000244

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00784

GnomAD3 exomes AF: 0.00426 AC: 874 AN: 205036 Hom.: 154 AF XY: 0.00414 AC XY: 460 AN XY: 111138

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.00337

Gnomad ASJ exome AF: 0.00445

Gnomad EAS exome AF: 0.00378

Gnomad SAS exome AF: 0.00456

Gnomad FIN exome AF: 0.00209

Gnomad NFE exome AF: 0.00380

Gnomad OTH exome AF: 0.00414

GnomAD4 exome AF: 0.00471 AC: 5145 AN: 1092930 Hom.: 62 AF XY: 0.00487 AC XY: 2641 AN XY: 541746

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00685

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.00982

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00408

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00651

GnomAD4 genome AF: 0.00678 AC: 812 AN: 119826 Hom.: 10 Cov.: 0 AF XY: 0.00631 AC XY: 364 AN XY: 57720

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00109

Gnomad4 EAS AF: 0.00725

Gnomad4 SAS AF: 0.00506

Gnomad4 FIN AF: 0.000244

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.00774

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DICER1-related tumor predisposition Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 10, 2023	- -

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 19, 2019

- -

Euthyroid goiter Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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: rs199508452; hg19: chr14-95566101;