rs146861504
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_024782.3(NHEJ1):c.560A>G(p.Asn187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,611,718 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00068 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 3 hom. )
Consequence
NHEJ1
NM_024782.3 missense
NM_024782.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 2.32
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004739493).
BP6
?
Variant 2-219146708-T-C is Benign according to our data. Variant chr2-219146708-T-C is described in ClinVar as [Benign]. Clinvar id is 568300.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-219146708-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000676 (103/152292) while in subpopulation NFE AF= 0.000603 (41/68020). AF 95% confidence interval is 0.000457. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHEJ1 | NM_024782.3 | c.560A>G | p.Asn187Ser | missense_variant | 5/8 | ENST00000356853.10 | |
NHEJ1 | NM_001377499.1 | c.560A>G | p.Asn187Ser | missense_variant | 5/8 | ||
NHEJ1 | NM_001377498.1 | c.560A>G | p.Asn187Ser | missense_variant | 5/8 | ||
NHEJ1 | NR_165304.1 | n.656A>G | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHEJ1 | ENST00000356853.10 | c.560A>G | p.Asn187Ser | missense_variant | 5/8 | 1 | NM_024782.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000683 AC: 104AN: 152174Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251426Hom.: 0 AF XY: 0.000846 AC XY: 115AN XY: 135890
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GnomAD4 exome AF: 0.000538 AC: 785AN: 1459426Hom.: 3 Cov.: 29 AF XY: 0.000566 AC XY: 411AN XY: 726244
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GnomAD4 genome ? AF: 0.000676 AC: 103AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74462
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Cernunnos-XLF deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;.
Polyphen
0.0
.;B;.;.
Vest4
MVP
MPC
0.041
ClinPred
T
GERP RS
Varity_R
gMVP
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