rs1805790

chr8-89962473-T-Cchr8-89962473-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.994+1937A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,072 control chromosomes in the GnomAD database, including 7,474 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 (7474 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.994+1937A>G		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.994+1937A>G		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46825 AN: 151954 Hom.: 7466 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.308 AC: 46853 AN: 152072 Hom.: 7474 Cov.: 32 AF XY: 0.313 AC XY: 23302 AN XY: 74338

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.326

Alfa AF: 0.311 Hom.: 953

Bravo AF: 0.300

Asia WGS AF: 0.421 AC: 1461 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1805790; hg19: chr8-90974701;