rs13078

Variant names:

• chr14-95090410-A-T
• rs13078
• NM_177438.3:c.*88T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-95090410-A-T
• chr14-95090410-A-C

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.*88T>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 0.83 in 1,469,042 control chromosomes in the GnomAD database, including 507,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (55908 hom., cov: 32)
  • Exomes 𝑓: 0.83 (452018 hom.)
• Consequence: DICER1 NM_177438.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.172
• Publications: 53 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=-0.93).
• BP6: Variant 14-95090410-A-T is Benign according to our data. Variant chr14-95090410-A-T is described in ClinVar as Benign. ClinVar VariationId is 315098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 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.*88T>A		3_prime_UTR	Exon 27 of 27	NP_803187.1	Q9UPY3-1
	DICER1	NM_001271282.3		c.*88T>A		3_prime_UTR	Exon 27 of 27	NP_001258211.1	Q9UPY3-1
	DICER1	NM_001291628.2		c.*88T>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.*88T>A		3_prime_UTR	Exon 27 of 27	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000393063.6	TSL:1	c.*88T>A		3_prime_UTR	Exon 29 of 29	ENSP00000376783.1	Q9UPY3-1
	DICER1	ENST00000527414.5	TSL:1	c.*88T>A		3_prime_UTR	Exon 27 of 27	ENSP00000435681.1	Q9UPY3-1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130197 AN: 152142 Hom.: 55862 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.827 AC: 1089142 AN: 1316782 Hom.: 452018 Cov.: 19 AF XY: 0.830 AC XY: 549471 AN XY: 662244

African (AFR) AF: 0.915 AC: 27693 AN: 30274

American (AMR) AF: 0.910 AC: 39952 AN: 43888

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 20196 AN: 25228

East Asian (EAS) AF: 0.956 AC: 37098 AN: 38788

South Asian (SAS) AF: 0.925 AC: 76282 AN: 82470

European-Finnish (FIN) AF: 0.808 AC: 41981 AN: 51962

Middle Eastern (MID) AF: 0.847 AC: 3279 AN: 3870

European-Non Finnish (NFE) AF: 0.808 AC: 796106 AN: 984756

Other (OTH) AF: 0.838 AC: 46555 AN: 55546

GnomAD4 genome AF: 0.856 AC: 130301 AN: 152260 Hom.: 55908 Cov.: 32 AF XY: 0.859 AC XY: 63958 AN XY: 74448

African (AFR) AF: 0.915 AC: 38019 AN: 41560

American (AMR) AF: 0.871 AC: 13319 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2796 AN: 3470

East Asian (EAS) AF: 0.959 AC: 4984 AN: 5196

South Asian (SAS) AF: 0.931 AC: 4494 AN: 4828

European-Finnish (FIN) AF: 0.811 AC: 8592 AN: 10598

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55351 AN: 67996

Other (OTH) AF: 0.830 AC: 1752 AN: 2112

Alfa AF: 0.823 Hom.: 28676

Bravo AF: 0.862

Asia WGS AF: 0.941 AC: 3272 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	DICER1-related tumor predisposition (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.44
PhyloP100		-0.17
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: rs13078; hg19: chr14-95556747; COSMIC: COSV100601717;