rs7157322

Positions:

• chr14-95116207-A-C
• chr14-95116207-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177438.3(DICER1):​c.1752+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,068 control chromosomes in the GnomAD database, including 16,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16004 hom., cov: 32)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.582

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-95116207-A-C is Benign according to our data. Variant chr14-95116207-A-C is described in ClinVar as [Benign]. Clinvar id is 676815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.1752+246T>G		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.1752+246T>G		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64975 AN: 151950 Hom.: 15963 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 65076 AN: 152068 Hom.: 16004 Cov.: 32 AF XY: 0.423 AC XY: 31471 AN XY: 74346

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.414

Alfa AF: 0.345 Hom.: 4634

Bravo AF: 0.443

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49

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: rs7157322; hg19: chr14-95582544;