chr14-95138791-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_177438.3(DICER1):​c.-45-5288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 131,652 control chromosomes in the GnomAD database, including 457 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 0.057 ( 457 hom., cov: 22)

Consequence

DICER1
NM_177438.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

1 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DICER1NM_177438.3 linkc.-45-5288C>T intron_variant Intron 1 of 26 ENST00000343455.8 NP_803187.1 Q9UPY3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DICER1ENST00000343455.8 linkc.-45-5288C>T intron_variant Intron 1 of 26 1 NM_177438.3 ENSP00000343745.3 Q9UPY3-1

Frequencies

GnomAD3 genomes
AF:
0.0568
AC:
7468
AN:
131568
Hom.:
461
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.0151
Gnomad AMI
AF:
0.0247
Gnomad AMR
AF:
0.0804
Gnomad ASJ
AF:
0.0750
Gnomad EAS
AF:
0.299
Gnomad SAS
AF:
0.213
Gnomad FIN
AF:
0.0290
Gnomad MID
AF:
0.0739
Gnomad NFE
AF:
0.0520
Gnomad OTH
AF:
0.0531
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0566
AC:
7455
AN:
131652
Hom.:
457
Cov.:
22
AF XY:
0.0600
AC XY:
3766
AN XY:
62756
show subpopulations
African (AFR)
AF:
0.0150
AC:
530
AN:
35268
American (AMR)
AF:
0.0800
AC:
1008
AN:
12606
Ashkenazi Jewish (ASJ)
AF:
0.0750
AC:
246
AN:
3282
East Asian (EAS)
AF:
0.299
AC:
1280
AN:
4282
South Asian (SAS)
AF:
0.213
AC:
794
AN:
3736
European-Finnish (FIN)
AF:
0.0290
AC:
196
AN:
6760
Middle Eastern (MID)
AF:
0.0649
AC:
17
AN:
262
European-Non Finnish (NFE)
AF:
0.0520
AC:
3270
AN:
62894
Other (OTH)
AF:
0.0543
AC:
93
AN:
1712
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
321
642
962
1283
1604
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
90
180
270
360
450
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0149
Hom.:
3
Bravo
AF:
0.0595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.8
DANN
Benign
0.69
PhyloP100
-1.4
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

Publications

Other links and lift over

dbSNP: rs12432281; hg19: chr14-95605128; COSMIC: COSV58629029; COSMIC: COSV58629029; API