chr14-95087805-T-C

Variant names:

• chr14-95087805-T-C
• rs1057035
• NM_177438.3:c.*2693A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177438.3(DICER1):​c.*2693A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 233,052 control chromosomes in the GnomAD database, including 10,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6358 hom., cov: 32)
  • Exomes 𝑓: 0.30 (4013 hom.)
• Consequence: DICER1 NM_177438.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.256
• Publications: 73 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-95087805-T-C is Benign according to our data. Variant chr14-95087805-T-C is described in ClinVar as Benign. ClinVar VariationId is 315063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 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.*2693A>G		3_prime_UTR	Exon 27 of 27	NP_803187.1	Q9UPY3-1
	DICER1	NM_001271282.3		c.*2693A>G		3_prime_UTR	Exon 27 of 27	NP_001258211.1	Q9UPY3-1
	DICER1	NM_001291628.2		c.*2693A>G		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.*2693A>G		3_prime_UTR	Exon 27 of 27	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000529720.2	TSL:1	c.*2693A>G		3_prime_UTR	Exon 30 of 30	ENSP00000433926.2	Q9UPY3-1
	DICER1	ENST00000531162.7	TSL:1	c.*2693A>G		3_prime_UTR	Exon 29 of 29	ENSP00000433060.3	Q9UPY3-1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39172 AN: 152014 Hom.: 6360 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.298 AC: 24079 AN: 80920 Hom.: 4013 Cov.: 0 AF XY: 0.297 AC XY: 11063 AN XY: 37190

African (AFR) AF: 0.0814 AC: 317 AN: 3892

American (AMR) AF: 0.336 AC: 839 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1684 AN: 5118

East Asian (EAS) AF: 0.112 AC: 1273 AN: 11398

South Asian (SAS) AF: 0.107 AC: 75 AN: 700

European-Finnish (FIN) AF: 0.288 AC: 19 AN: 66

Middle Eastern (MID) AF: 0.205 AC: 101 AN: 492

European-Non Finnish (NFE) AF: 0.355 AC: 17731 AN: 49990

Other (OTH) AF: 0.302 AC: 2040 AN: 6764

GnomAD4 genome AF: 0.257 AC: 39171 AN: 152132 Hom.: 6358 Cov.: 32 AF XY: 0.251 AC XY: 18665 AN XY: 74376

African (AFR) AF: 0.0799 AC: 3317 AN: 41530

American (AMR) AF: 0.318 AC: 4855 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3466

East Asian (EAS) AF: 0.135 AC: 700 AN: 5172

South Asian (SAS) AF: 0.0857 AC: 414 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3113 AN: 10564

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24624 AN: 67974

Other (OTH) AF: 0.270 AC: 570 AN: 2110

Alfa AF: 0.309 Hom.: 17218

Bravo AF: 0.256

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	DICER1-related tumor predisposition (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.55
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1057035; hg19: chr14-95554142;