rs746597527

chr14-95099758-ACACACACACACAC-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+21del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 149,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0048 (35 hom.)
  • Failed GnomAD Quality Control
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 14-95099758-ACACACACACACAC-A is Benign according to our data. Variant chr14-95099758-ACACACACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477188.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 = 0.00185 (278/149996) while in subpopulation AFR AF= 0.00458 (182/39724). AF 95% confidence interval is 0.00404. There are 0 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.4206+9_4206+21del		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.4206+9_4206+21del		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 277 AN: 149888 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00457

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00352

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00290

GnomAD3 exomes AF: 0.00819 AC: 1905 AN: 232686 Hom.: 137 AF XY: 0.00835 AC XY: 1059 AN XY: 126816

Gnomad AFR exome AF: 0.00475

Gnomad AMR exome AF: 0.00938

Gnomad ASJ exome AF: 0.00609

Gnomad EAS exome AF: 0.0297

Gnomad SAS exome AF: 0.0102

Gnomad FIN exome AF: 0.00738

Gnomad NFE exome AF: 0.00465

Gnomad OTH exome AF: 0.00672

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00483 AC: 6974 AN: 1443068 Hom.: 35 AF XY: 0.00510 AC XY: 3660 AN XY: 718046

Gnomad4 AFR exome AF: 0.00466

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00416

Gnomad4 EAS exome AF: 0.0536

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00792

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.00185 AC: 278 AN: 149996 Hom.: 0 Cov.: 0 AF XY: 0.00197 AC XY: 144 AN XY: 73270

Gnomad4 AFR AF: 0.00458

Gnomad4 AMR AF: 0.00132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00352

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00288

Alfa AF: 0.00174 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 15, 2019

- -

DICER1-related tumor predisposition Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 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: rs746597527; hg19: chr14-95566095;