14-95099771-C-CACACACACACACAA

Position:

• chr14-95099771-C-CACACACACACACAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_177438.3(DICER1):​c.4206+8_4206+9insTTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 26,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 14-95099771-C-CACACACACACACAA is Benign according to our data. Variant chr14-95099771-C-CACACACACACACAA is described in ClinVar as [Likely_benign]. Clinvar id is 477184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000522 (14/26844) while in subpopulation AFR AF= 0.00094 (13/13836). AF 95% confidence interval is 0.000556. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000523 AC: 14 AN: 26764 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000477

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000255 AC: 7 AN: 274866 Hom.: 0 Cov.: 34 AF XY: 0.0000223 AC XY: 3 AN XY: 134704

Gnomad4 AFR exome AF: 0.000386

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000170

GnomAD4 genome AF: 0.000522 AC: 14 AN: 26844 Hom.: 0 Cov.: 30 AF XY: 0.000690 AC XY: 9 AN XY: 13040

Gnomad4 AFR AF: 0.000940

Gnomad4 AMR AF: 0.000478

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DICER1-related tumor predisposition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 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;