rs12889800

chr14-95152561-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.-46+4669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,264 control chromosomes in the GnomAD database, including 415 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 0.065 (415 hom., cov: 32)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.-46+4669A>G		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.-46+4669A>G		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9891 AN: 152146 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0631

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

GnomAD4 genome AF: 0.0650 AC: 9901 AN: 152264 Hom.: 415 Cov.: 32 AF XY: 0.0634 AC XY: 4722 AN XY: 74464

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0456

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0605 Hom.: 57

Bravo AF: 0.0667

Asia WGS AF: 0.0140 AC: 49 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.068
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12889800; hg19: chr14-95618898;