rs7585742
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_024782.3(NHEJ1):c.391-59C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,573,286 control chromosomes in the GnomAD database, including 293,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.50 ( 21570 hom., cov: 33)
Exomes 𝑓: 0.61 ( 272006 hom. )
Consequence
NHEJ1
NM_024782.3 intron
NM_024782.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.32
Genes affected
NHEJ1 (HGNC:25737): (non-homologous end joining factor 1) Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders. [provided by RefSeq, Jul 2008]
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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=-0.88).
BP6
?
Variant 2-219147854-G-C is Benign according to our data. Variant chr2-219147854-G-C is described in ClinVar as [Benign]. Clinvar id is 1243280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHEJ1 | NM_024782.3 | c.391-59C>G | intron_variant | ENST00000356853.10 | |||
NHEJ1 | NM_001377498.1 | c.391-59C>G | intron_variant | ||||
NHEJ1 | NM_001377499.1 | c.391-59C>G | intron_variant | ||||
NHEJ1 | NR_165304.1 | n.487-59C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHEJ1 | ENST00000356853.10 | c.391-59C>G | intron_variant | 1 | NM_024782.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.503 AC: 76427AN: 151992Hom.: 21570 Cov.: 33
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GnomAD4 exome AF: 0.612 AC: 869417AN: 1421178Hom.: 272006 AF XY: 0.612 AC XY: 433586AN XY: 708858
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GnomAD4 genome ? AF: 0.502 AC: 76430AN: 152108Hom.: 21570 Cov.: 33 AF XY: 0.505 AC XY: 37574AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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