rs12881840

Positions:

• chr14-95101666-C-T

Variant summary

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

The NM_177438.3(DICER1):​c.4050+1680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 152,258 control chromosomes in the GnomAD database, including 411 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 0.064 (411 hom., cov: 32)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3	c.4050+1680G>A		intron_variant		ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.4050+1680G>A		intron_variant		1	NM_177438.3	ENSP00000343745	P1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9792 AN: 152140 Hom.: 408 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0638

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

GnomAD4 genome AF: 0.0644 AC: 9802 AN: 152258 Hom.: 411 Cov.: 32 AF XY: 0.0628 AC XY: 4673 AN XY: 74426

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0547 Hom.: 56

Bravo AF: 0.0660

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.46

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: rs12881840; hg19: chr14-95568003;