rs763704682

Positions:

• chr14-95099771-C-CACAA
• chr14-95099771-C-CACAAAA
• chr14-95099771-C-CACACAA
• chr14-95099771-C-CACACAAAA
• chr14-95099771-C-CACACACAA
• chr14-95099771-C-CACACACAAAA
• chr14-95099771-C-CACACACACAA
• chr14-95099771-C-CACACACACACAA
• chr14-95099771-C-CACACACACACACAA
• chr14-95099771-C-CACACACACACACACAA
• chr14-95099771-C-CACACACACACACACACAA
• chr14-95099771-C-CACACACACACACACACACACACAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000343455.8(DICER1):​c.4206+8_4206+9insTTGT variant causes a 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 ENST00000343455.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.425

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 14-95099771-C-CACAA is Benign according to our data. Variant chr14-95099771-C-CACAA is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
DICER1	NM_177438.3	c.4206+8_4206+9insTTGT		intron_variant		ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.4206+8_4206+9insTTGT		intron_variant		1	NM_177438.3	ENSP00000343745	P1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 1413 AN: 26746 Hom.: 54 Cov.: 30

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

GnomAD3 exomes AF: 0.00329 AC: 561 AN: 170614 Hom.: 183 AF XY: 0.00241 AC XY: 223 AN XY: 92356

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 SAS exome AF: 0.000613

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.: 44 Cov.: 34 AF XY: 0.00432 AC XY: 581 AN XY: 134510

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.000654

Gnomad4 EAS exome AF: 0.000413

Gnomad4 SAS exome AF: 0.00310

Gnomad4 FIN exome AF: 0.000554

Gnomad4 NFE exome AF: 0.000935

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.0528 AC: 1416 AN: 26826 Hom.: 52 Cov.: 30 AF XY: 0.0491 AC XY: 640 AN XY: 13032

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00292

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00339

Gnomad4 OTH AF: 0.0595

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

DICER1-related tumor predisposition Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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: rs763704682; hg19: chr14-95566108;