chr14-95097375-T-C

Variant names:

• chr14-95097375-T-C
• rs1209904
• NM_177438.3:c.4207-662A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177438.3(DICER1):​c.4207-662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,014 control chromosomes in the GnomAD database, including 43,762 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 (43762 hom., cov: 31)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 11 publications found

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]

DICER1 Gene-Disease associations (from GenCC):

• DICER1-related tumor predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pleuropulmonary blastoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• DICER1 syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3	c.4207-662A>G		intron_variant	Intron 22 of 26	ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.4207-662A>G		intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114906 AN: 151896 Hom.: 43741 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.724

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.756 AC: 114975 AN: 152014 Hom.: 43762 Cov.: 31 AF XY: 0.763 AC XY: 56694 AN XY: 74310

African (AFR) AF: 0.679 AC: 28115 AN: 41418

American (AMR) AF: 0.820 AC: 12519 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.959 AC: 4973 AN: 5186

South Asian (SAS) AF: 0.913 AC: 4400 AN: 4820

European-Finnish (FIN) AF: 0.765 AC: 8079 AN: 10558

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.764 AC: 51903 AN: 67980

Other (OTH) AF: 0.745 AC: 1571 AN: 2110

Alfa AF: 0.765 Hom.: 34278

Bravo AF: 0.755

Asia WGS AF: 0.913 AC: 3170 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1209904; hg19: chr14-95563712;