rs7011299

Variant names:

• chr8-90001011-C-G
• rs7011299
• ENST00000396252.6:n.-230+2101G>C

Variant summary

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

The ENST00000396252.6(NBN):​n.-230+2101G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,192 control chromosomes in the GnomAD database, including 7,514 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 0.31 (7514 hom., cov: 33)
• Consequence: NBN ENST00000396252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.-230+2101G>C		intron_variant	Intron 1 of 18	5		ENSP00000379551.2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47003 AN: 152074 Hom.: 7506 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.309 AC: 47031 AN: 152192 Hom.: 7514 Cov.: 33 AF XY: 0.315 AC XY: 23408 AN XY: 74428

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.329

Alfa AF: 0.320 Hom.: 1003

Bravo AF: 0.301

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7011299; hg19: chr8-91013239;