rs587781092
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002485.5(NBN):c.481-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000616 in 1,575,712 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000065 ( 2 hom. )
Consequence
NBN
NM_002485.5 intron
NM_002485.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.592
Genes affected
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 8-89978341-T-C is Benign according to our data. Variant chr8-89978341-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 138429.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000646 (92/1423540) while in subpopulation AMR AF= 0.00125 (56/44638). AF 95% confidence interval is 0.000991. There are 2 homozygotes in gnomad4_exome. There are 38 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.481-18A>G | intron_variant | ENST00000265433.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.481-18A>G | intron_variant | 1 | NM_002485.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000211 AC: 53AN: 250626Hom.: 2 AF XY: 0.000148 AC XY: 20AN XY: 135544
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GnomAD4 exome AF: 0.0000646 AC: 92AN: 1423540Hom.: 2 Cov.: 27 AF XY: 0.0000535 AC XY: 38AN XY: 710242
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74350
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2015 | The c.481-18A>G intronic alteration consists of a A to G substitution 18 nucleotides before coding exon 5 in the NBN gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2014 | 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. - |
Microcephaly, normal intelligence and immunodeficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
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