14-95112338-T-C

Position:

• chr14-95112338-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177438.3(DICER1):​c.2041-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,053,282 control chromosomes in the GnomAD database, including 13,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3612 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9518 hom.)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0620

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-95112338-T-C is Benign according to our data. Variant chr14-95112338-T-C is described in ClinVar as [Benign]. Clinvar id is 676900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3	c.2041-91A>G		intron_variant		ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.2041-91A>G		intron_variant		1	NM_177438.3	ENSP00000343745	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27712 AN: 151904 Hom.: 3605 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.118 AC: 106705 AN: 901260 Hom.: 9518 AF XY: 0.119 AC XY: 55317 AN XY: 464654

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.0981

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0865

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.183 AC: 27755 AN: 152022 Hom.: 3612 Cov.: 32 AF XY: 0.186 AC XY: 13791 AN XY: 74302

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.153

Alfa AF: 0.143 Hom.: 385

Bravo AF: 0.193

Asia WGS AF: 0.253 AC: 878 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2297730; hg19: chr14-95578675; COSMIC: COSV58616604; COSMIC: COSV58616604;