chr5-31429466-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001382508.1(DROSHA):c.3216+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,603,348 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0084 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 117 hom. )
Consequence
DROSHA
NM_001382508.1 intron
NM_001382508.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.507
Genes affected
DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 5-31429466-T-C is Benign according to our data. Variant chr5-31429466-T-C is described in ClinVar as [Benign]. Clinvar id is 780954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00845 (1286/152212) while in subpopulation EAS AF= 0.0334 (173/5180). AF 95% confidence interval is 0.0293. There are 12 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1286 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DROSHA | NM_001382508.1 | c.3216+9A>G | intron_variant | ENST00000344624.8 | |||
DROSHA | NM_001100412.2 | c.3105+9A>G | intron_variant | ||||
DROSHA | NM_013235.5 | c.3216+9A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DROSHA | ENST00000344624.8 | c.3216+9A>G | intron_variant | 5 | NM_001382508.1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00845 AC: 1285AN: 152094Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00903 AC: 2184AN: 241758Hom.: 40 AF XY: 0.0101 AC XY: 1325AN XY: 130888
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GnomAD4 exome AF: 0.00592 AC: 8587AN: 1451136Hom.: 117 Cov.: 30 AF XY: 0.00667 AC XY: 4815AN XY: 721368
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GnomAD4 genome AF: 0.00845 AC: 1286AN: 152212Hom.: 12 Cov.: 32 AF XY: 0.00863 AC XY: 642AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DROSHA-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at