8-89972575-G-C

Position:

• chr8-89972575-G-C

Variant summary

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

The NM_002485.5(NBN):​c.585-1285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,168 control chromosomes in the GnomAD database, including 5,303 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 0.25 (5303 hom., cov: 33)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.585-1285C>G		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.585-1285C>G		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37638 AN: 152048 Hom.: 5300 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.247 AC: 37642 AN: 152168 Hom.: 5303 Cov.: 33 AF XY: 0.254 AC XY: 18897 AN XY: 74392

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.257

Alfa AF: 0.174 Hom.: 389

Bravo AF: 0.233

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs741778; hg19: chr8-90984803;