14-95099771-C-CACACACACACAA

Position:

• chr14-95099771-C-CACACACACACAA

Variant summary

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

The ENST00000343455.8(DICER1):​c.4206+8_4206+9insTTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 26,832 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (8 hom., cov: 30)
  • Exomes 𝑓: 0.00036 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: DICER1 ENST00000343455.8 intron
• Clinical Significance: 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-CACACACACACAA is Benign according to our data. Variant chr14-95099771-C-CACACACACACAA is described in ClinVar as [Benign]. Clinvar id is 242103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00779 (209/26832) while in subpopulation AFR AF= 0.0149 (206/13824). AF 95% confidence interval is 0.0132. There are 8 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00774 AC: 207 AN: 26752 Hom.: 7 Cov.: 30

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000953

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: 0.00243

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000360 AC: 99 AN: 274838 Hom.: 2 Cov.: 34 AF XY: 0.000349 AC XY: 47 AN XY: 134690

Gnomad4 AFR exome AF: 0.00658

Gnomad4 AMR exome AF: 0.00100

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: 0.0000141

Gnomad4 OTH exome AF: 0.000511

GnomAD4 genome AF: 0.00779 AC: 209 AN: 26832 Hom.: 8 Cov.: 30 AF XY: 0.00691 AC XY: 90 AN XY: 13034

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.000955

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: 0.00238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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;