rs2142097

Variant names:

• chr8-89932804-T-C
• rs2142097
• ENST00000697293:c.*2778A>G

Variant summary

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

The ENST00000517337(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 ENST00000517337 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000697293	c.*2778A>G		3_prime_UTR_variant	Exon 17 of 17			ENSP00000513230.1
NBN	ENST00000697308	c.*2778A>G		3_prime_UTR_variant	Exon 15 of 15			ENSP00000513243.1
NBN	ENST00000697307	c.*2778A>G		3_prime_UTR_variant	Exon 14 of 14			ENSP00000513242.1

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;