chr14-95086612-G-A

Variant names:

• chr14-95086612-G-A
• rs11556997
• NM_177438.3:c.*3886C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_177438.3(DICER1):​c.*3886C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 233,206 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (1 hom.)
• Consequence: DICER1 NM_177438.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.294
• Publications: 0 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=-0.8).
• BP6: Variant 14-95086612-G-A is Benign according to our data. Variant chr14-95086612-G-A is described in ClinVar as Benign. ClinVar VariationId is 315047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00415 (631/152220) while in subpopulation SAS AF = 0.0141 (68/4826). AF 95% confidence interval is 0.0114. There are 5 homozygotes in GnomAd4. There are 373 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 631 AD,Unknown gene.

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.*3886C>T		3_prime_UTR	Exon 27 of 27	NP_803187.1	Q9UPY3-1
	DICER1	NM_001271282.3		c.*3886C>T		3_prime_UTR	Exon 27 of 27	NP_001258211.1	Q9UPY3-1
	DICER1	NM_001291628.2		c.*3886C>T		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.*3886C>T		3_prime_UTR	Exon 27 of 27	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000529720.2	TSL:1	c.*3886C>T		3_prime_UTR	Exon 30 of 30	ENSP00000433926.2	Q9UPY3-1
	DICER1	ENST00000531162.7	TSL:1	c.*3886C>T		3_prime_UTR	Exon 29 of 29	ENSP00000433060.3	Q9UPY3-1

Frequencies

GnomAD3 genomes AF: 0.00414 AC: 630 AN: 152102 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00340 AC: 275 AN: 80986 Hom.: 1 Cov.: 0 AF XY: 0.00367 AC XY: 137 AN XY: 37304

African (AFR) AF: 0.000516 AC: 2 AN: 3878

American (AMR) AF: 0.00160 AC: 4 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.00392 AC: 20 AN: 5106

East Asian (EAS) AF: 0.00 AC: 0 AN: 11262

South Asian (SAS) AF: 0.0230 AC: 16 AN: 696

European-Finnish (FIN) AF: 0.0145 AC: 7 AN: 482

Middle Eastern (MID) AF: 0.0143 AC: 7 AN: 488

European-Non Finnish (NFE) AF: 0.00405 AC: 202 AN: 49832

Other (OTH) AF: 0.00252 AC: 17 AN: 6746

GnomAD4 genome AF: 0.00415 AC: 631 AN: 152220 Hom.: 5 Cov.: 33 AF XY: 0.00501 AC XY: 373 AN XY: 74420

African (AFR) AF: 0.000842 AC: 35 AN: 41546

American (AMR) AF: 0.00320 AC: 49 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4826

European-Finnish (FIN) AF: 0.0181 AC: 191 AN: 10576

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00381 AC: 259 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00325 Hom.: 1

Bravo AF: 0.00283

Asia WGS AF: 0.00550 AC: 19 AN: 3468

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	-0.80
CADD	Benign	0.43
DANN	Benign	0.74
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11556997; hg19: chr14-95552949; COSMIC: COSV107402278;