rs2021881

Positions:

• chr8-89933257-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517337(NBN):​c.*2325G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 183,692 control chromosomes in the GnomAD database, including 9,265 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 (7469 hom., cov: 33)
  • Exomes 𝑓: 0.33 (1796 hom.)
• Consequence: NBN ENST00000517337 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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]

NBN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• 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
		n.89933257C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000697293	c.*2325G>A		3_prime_UTR_variant	17/17			ENSP00000513230.1
NBN	ENST00000697308	c.*2325G>A		3_prime_UTR_variant	15/15			ENSP00000513243.1
NBN	ENST00000697307	c.*2325G>A		3_prime_UTR_variant	14/14			ENSP00000513242.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47555 AN: 151950 Hom.: 7459 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.334 AC: 10565 AN: 31624 Hom.: 1796 AF XY: 0.333 AC XY: 4845 AN XY: 14558

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.313 AC: 47593 AN: 152068 Hom.: 7469 Cov.: 33 AF XY: 0.312 AC XY: 23213 AN XY: 74334

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.303

Alfa AF: 0.329 Hom.: 1731

Bravo AF: 0.307

Asia WGS AF: 0.308 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2021881; hg19: chr8-90945485;