8-89957793-T-G

Position:

• chr8-89957793-T-G

Variant summary

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

The NM_002485.5(NBN):​c.1124+932A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,982 control chromosomes in the GnomAD database, including 22,060 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 (22060 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBN	NM_002485.5	c.1124+932A>C		intron_variant		ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.1124+932A>C		intron_variant		1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77290 AN: 151864 Hom.: 21991 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.509 AC: 77429 AN: 151982 Hom.: 22060 Cov.: 32 AF XY: 0.515 AC XY: 38282 AN XY: 74294

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.491

Alfa AF: 0.457 Hom.: 2209

Bravo AF: 0.526

Asia WGS AF: 0.622 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7010210; hg19: chr8-90970021;