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. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• idiopathic aplastic anemia

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.0373 AC: 1539 AN: 41216

American (AMR) AF: 0.0522 AC: 793 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 119 AN: 3464

East Asian (EAS) AF: 0.143 AC: 738 AN: 5160

South Asian (SAS) AF: 0.0458 AC: 220 AN: 4802

European-Finnish (FIN) AF: 0.0992 AC: 1022 AN: 10298

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5946 AN: 67882

Other (OTH) AF: 0.0624 AC: 131 AN: 2100

Alfa AF: 0.0674 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
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs13312840; hg19: chr8-90997909;