chr8-89998845-C-G

Position:

• chr8-89998845-C-G

Variant summary

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

The variant allele was found at a frequency of 0.402 in 150,602 control chromosomes in the GnomAD database, including 12,721 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 0.40 (12721 hom., cov: 29)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

Genes affected

(HGNC:):

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.89998845C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000396252.6	n.-230+4267G>C		intron_variant		5		ENSP00000379551.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60393 AN: 150500 Hom.: 12697 Cov.: 29

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.402 AC: 60472 AN: 150602 Hom.: 12721 Cov.: 29 AF XY: 0.404 AC XY: 29691 AN XY: 73466

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.417

Alfa AF: 0.365 Hom.: 1290

Bravo AF: 0.408

Asia WGS AF: 0.465 AC: 1617 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	0.41
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2097825; hg19: chr8-91011073;