rs6470522

chr8-89942253-A-Gchr8-89942253-A-T

Variant summary

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

The NM_002485.5(NBN):c.2184+1000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,164 control chromosomes in the GnomAD database, including 56,656 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 0.86 (56656 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.2184+1000T>C		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.2184+1000T>C		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130762 AN: 152046 Hom.: 56592 Cov.: 32

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.860 AC: 130883 AN: 152164 Hom.: 56656 Cov.: 32 AF XY: 0.858 AC XY: 63810 AN XY: 74368

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.855

Alfa AF: 0.837 Hom.: 104037

Bravo AF: 0.863

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.1
Dann	Benign	0.70

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: rs6470522; hg19: chr8-90954481;