rs1235369

Positions:

• chr8-89961510-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002485.5(NBN):​c.995-2656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,296 control chromosomes in the GnomAD database, including 62 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 0.027 (62 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4096/152296) while in subpopulation NFE AF= 0.039 (2653/68024). AF 95% confidence interval is 0.0378. There are 62 homozygotes in gnomad4. There are 1981 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 62 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBN	NM_002485.5	c.995-2656T>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.995-2656T>C		intron_variant		1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4096 AN: 152178 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00688

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0269 AC: 4096 AN: 152296 Hom.: 62 Cov.: 32 AF XY: 0.0266 AC XY: 1981 AN XY: 74484

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0300 Hom.: 7

Bravo AF: 0.0241

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.76

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: rs1235369; hg19: chr8-90973738;