chr14-95086459-C-T

Variant names:

• chr14-95086459-C-T
• rs112079219
• NM_177438.3:c.*4039G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177438.3(DICER1):​c.*4039G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 233,276 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (305 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (39 hom.)
• Consequence: DICER1 NM_177438.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.658
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 14-95086459-C-T is Benign according to our data. Variant chr14-95086459-C-T is described in ClinVar as Benign. ClinVar VariationId is 315044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DICER1	NM_177438.3	MANE Select	c.*4039G>A		3_prime_UTR	Exon 27 of 27	NP_803187.1	Q9UPY3-1
	DICER1	NM_001271282.3		c.*4039G>A		3_prime_UTR	Exon 27 of 27	NP_001258211.1	Q9UPY3-1
	DICER1	NM_001291628.2		c.*4039G>A		3_prime_UTR	Exon 27 of 27	NP_001278557.1	Q9UPY3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DICER1	ENST00000343455.8	TSL:1 MANE Select	c.*4039G>A		3_prime_UTR	Exon 27 of 27	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000529720.2	TSL:1	c.*4039G>A		3_prime_UTR	Exon 30 of 30	ENSP00000433926.2	Q9UPY3-1
	DICER1	ENST00000531162.7	TSL:1	c.*4039G>A		3_prime_UTR	Exon 29 of 29	ENSP00000433060.3	Q9UPY3-1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5043 AN: 152132 Hom.: 304 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00734 AC: 595 AN: 81026 Hom.: 39 Cov.: 0 AF XY: 0.00670 AC XY: 250 AN XY: 37310

African (AFR) AF: 0.123 AC: 478 AN: 3880

American (AMR) AF: 0.00962 AC: 24 AN: 2494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5112

East Asian (EAS) AF: 0.00 AC: 0 AN: 11270

South Asian (SAS) AF: 0.00 AC: 0 AN: 698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 484

Middle Eastern (MID) AF: 0.00615 AC: 3 AN: 488

European-Non Finnish (NFE) AF: 0.000120 AC: 6 AN: 49854

Other (OTH) AF: 0.0125 AC: 84 AN: 6746

GnomAD4 genome AF: 0.0332 AC: 5055 AN: 152250 Hom.: 305 Cov.: 33 AF XY: 0.0321 AC XY: 2392 AN XY: 74444

African (AFR) AF: 0.116 AC: 4823 AN: 41522

American (AMR) AF: 0.0114 AC: 175 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68020

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0302 Hom.: 30

Bravo AF: 0.0379

Asia WGS AF: 0.00838 AC: 30 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DICER1-related tumor predisposition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.66
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: rs112079219; hg19: chr14-95552796;