chr5-177511788-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016222.4(DDX41):c.*3C>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 0.00146 in 1,613,966 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 23 hom., cov: 33)
Exomes 𝑓: 0.00076 ( 21 hom. )
Consequence
DDX41
NM_016222.4 3_prime_UTR
NM_016222.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.379
Genes affected
DDX41 (HGNC:18674): (DEAD-box helicase 41) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD box protein family and interacts with several spliceosomal proteins. In addition, the encoded protein may recognize the bacterial second messengers cyclic di-GMP and cyclic di-AMP, resulting in the induction of genes involved in the innate immune response. [provided by RefSeq, Jan 2017]
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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=-0.8).
BP6
?
Variant 5-177511788-G-A is Benign according to our data. Variant chr5-177511788-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00816 (1243/152274) while in subpopulation AFR AF= 0.0286 (1187/41554). AF 95% confidence interval is 0.0272. There are 23 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1235 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX41 | NM_016222.4 | c.*3C>T | 3_prime_UTR_variant | 17/17 | ENST00000330503.12 | ||
DDX41 | NM_001321732.2 | c.*3C>T | 3_prime_UTR_variant | 16/16 | |||
DDX41 | NM_001321830.2 | c.*3C>T | 3_prime_UTR_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX41 | ENST00000330503.12 | c.*3C>T | 3_prime_UTR_variant | 17/17 | 1 | NM_016222.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00812 AC: 1235AN: 152156Hom.: 22 Cov.: 33
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GnomAD3 exomes AF: 0.00191 AC: 477AN: 249758Hom.: 4 AF XY: 0.00141 AC XY: 191AN XY: 135140
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GnomAD4 exome AF: 0.000757 AC: 1106AN: 1461692Hom.: 21 Cov.: 33 AF XY: 0.000668 AC XY: 486AN XY: 727118
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 07, 2020 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 22, 2022 | See Variant Classification Assertion Criteria. - |
DDX41-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 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). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at