8-89939044-C-G

Position:

• chr8-89939044-C-G

Variant summary

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

The NM_002485.5(NBN):​c.2185-1969G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,946 control chromosomes in the GnomAD database, including 13,745 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 (13745 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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]

NBN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBN	NM_002485.5	c.2185-1969G>C		intron_variant		ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.2185-1969G>C		intron_variant		1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61210 AN: 151828 Hom.: 13706 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.403 AC: 61306 AN: 151946 Hom.: 13745 Cov.: 32 AF XY: 0.400 AC XY: 29732 AN XY: 74268

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.368

Alfa AF: 0.364 Hom.: 1335

Bravo AF: 0.412

Asia WGS AF: 0.359 AC: 1248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.62

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: rs2735387; hg19: chr8-90951272;