rs7011299

Positions:

• chr8-90001011-C-G

Variant summary

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

The ENST00000396252.6(NBN):​c.-230+2101G>C variant causes a intron, NMD transcript 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, NMD_transcript
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000396252.6	c.-230+2101G>C		intron_variant, NMD_transcript_variant		5		ENSP00000379551

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;