ENST00000697292.1:c.*39-3331T>A

Variant names:

• chr8-89928672-A-T
• rs1881469
• ENST00000697292.1:c.*39-3331T>A

Variant summary

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

The ENST00000697292.1(NBN):​c.*39-3331T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,980 control chromosomes in the GnomAD database, including 21,986 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 0.51 (21986 hom., cov: 31)
• Consequence: NBN ENST00000697292.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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	ENST00000697292.1	c.*39-3331T>A		intron_variant	Intron 16 of 16			ENSP00000513229.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77438 AN: 151864 Hom.: 21924 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.510 AC: 77577 AN: 151980 Hom.: 21986 Cov.: 31 AF XY: 0.509 AC XY: 37789 AN XY: 74268

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.495

Alfa AF: 0.462 Hom.: 2224

Bravo AF: 0.530

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1881469; hg19: chr8-90940900;