rs13312840

Variant names:

• chr8-89985681-A-G
• rs13312840
• ENST00000396252.6:n.-229-708T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-89985681-A-G
• chr8-89985681-A-T

Variant summary

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

The ENST00000396252.6(NBN):​n.-229-708T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 151,326 control chromosomes in the GnomAD database, including 443 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 0.070 (443 hom., cov: 31)
• Consequence: NBN ENST00000396252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000396252.6	n.-229-708T>C		intron_variant	Intron 1 of 18	5		ENSP00000379551.2

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10569 AN: 151228 Hom.: 442 Cov.: 31

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0620

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

GnomAD4 genome AF: 0.0698 AC: 10563 AN: 151326 Hom.: 443 Cov.: 31 AF XY: 0.0708 AC XY: 5231 AN XY: 73890

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0344

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0683 Hom.: 60

Bravo AF: 0.0658

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13312840; hg19: chr8-90997909;