rs2734823

chr8-89931500-A-G

Variant summary

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

The ENST00000697293.1(NBN):c.*4082T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,972 control chromosomes in the GnomAD database, including 24,146 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 0.53 (24146 hom., cov: 32)
• Consequence: NBN ENST00000697293.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 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.*4082T>C		3_prime_UTR_variant	17/17	4
NBN	ENST00000697293.1	c.*4082T>C		3_prime_UTR_variant	17/17
NBN	ENST00000697298.1	c.*4082T>C		3_prime_UTR_variant	18/18

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80319 AN: 151854 Hom.: 24074 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.529 AC: 80467 AN: 151972 Hom.: 24146 Cov.: 32 AF XY: 0.528 AC XY: 39203 AN XY: 74268

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.504

Alfa AF: 0.470 Hom.: 2443

Bravo AF: 0.550

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.77
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2734823; hg19: chr8-90943728;