rs2142097

Positions:

• chr8-89932804-T-C

Variant summary

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

The ENST00000697293.1(NBN):​c.*2778A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,070 control chromosomes in the GnomAD database, including 6,240 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 0.28 (6240 hom., cov: 32)
• Consequence: NBN ENST00000697293.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000517337.2	c.*2778A>G		3_prime_UTR_variant	17/17	4
NBN	ENST00000697293.1	c.*2778A>G		3_prime_UTR_variant	17/17
NBN	ENST00000697298.1	c.*2778A>G		3_prime_UTR_variant	18/18

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41892 AN: 151952 Hom.: 6235 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.276 AC: 41904 AN: 152070 Hom.: 6240 Cov.: 32 AF XY: 0.276 AC XY: 20509 AN XY: 74316

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.279

Alfa AF: 0.313 Hom.: 4666

Bravo AF: 0.264

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
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: rs2142097; hg19: chr8-90945032;