rs2735385
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002485.5(NBN):c.2185-421G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 195,152 control chromosomes in the GnomAD database, including 9,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.31 ( 7495 hom., cov: 32)
Exomes 𝑓: 0.29 ( 2047 hom. )
Consequence
NBN
NM_002485.5 intron
NM_002485.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0870
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.2185-421G>T | intron_variant | ENST00000265433.8 | NP_002476.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.2185-421G>T | intron_variant | 1 | NM_002485.5 | ENSP00000265433.4 |
Frequencies
GnomAD3 genomes AF: 0.314 AC: 47696AN: 151954Hom.: 7486 Cov.: 32
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GnomAD4 exome AF: 0.289 AC: 12446AN: 43078Hom.: 2047 AF XY: 0.287 AC XY: 6546AN XY: 22824
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GnomAD4 genome AF: 0.314 AC: 47731AN: 152074Hom.: 7495 Cov.: 32 AF XY: 0.313 AC XY: 23259AN XY: 74336
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ClinVar
Not reported inComputational 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