8-89938875-C-T

Position:

• chr8-89938875-C-T

Variant summary

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

The NM_002485.5(NBN):​c.2185-1800G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,090 control chromosomes in the GnomAD database, including 6,890 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 0.30 (6890 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.2185-1800G>A		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.2185-1800G>A		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45654 AN: 151972 Hom.: 6881 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.300 AC: 45685 AN: 152090 Hom.: 6890 Cov.: 32 AF XY: 0.300 AC XY: 22339 AN XY: 74346

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.286

Alfa AF: 0.315 Hom.: 970

Bravo AF: 0.294

Asia WGS AF: 0.302 AC: 1051 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.0
DANN	Benign	0.64

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: rs2735386; hg19: chr8-90951103;