14-95099219-T-C

Position:

• chr14-95099219-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177438.3(DICER1):​c.4206+561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,064 control chromosomes in the GnomAD database, including 43,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (43940 hom., cov: 31)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3	c.4206+561A>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.4206+561A>G		intron_variant		1	NM_177438.3	ENSP00000343745	P1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115157 AN: 151946 Hom.: 43918 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.758 AC: 115229 AN: 152064 Hom.: 43940 Cov.: 31 AF XY: 0.764 AC XY: 56831 AN XY: 74348

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.744

Alfa AF: 0.757 Hom.: 9707

Bravo AF: 0.756

Asia WGS AF: 0.919 AC: 3196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.66

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: rs1187655; hg19: chr14-95565556;