rs376041812
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_177438.3(DICER1):c.4207-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,599,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_177438.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4207-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000343455.8 | NP_803187.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4207-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_177438.3 | ENSP00000343745 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000120 AC: 26AN: 217140Hom.: 0 AF XY: 0.0000765 AC XY: 9AN XY: 117650
GnomAD4 exome AF: 0.000248 AC: 359AN: 1446862Hom.: 0 Cov.: 31 AF XY: 0.000227 AC XY: 163AN XY: 718716
GnomAD4 genome AF: 0.000145 AC: 22AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74314
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 25, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 15, 2022 | The frequency of this variant in the general population, 0.00025 (27/107852 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, this variant has been reported in an individual with an unspecified cancer (PMID: 21266384 (2011)). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect DICER1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. - |
DICER1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 15, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
DICER1-related tumor predisposition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at