rs1805812

Variant names:

• chr8-89952825-T-C
• rs1805812
• NM_002485.5:c.1845+419A>G

Variant summary

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

The NM_002485.5(NBN):​c.1845+419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 152,192 control chromosomes in the GnomAD database, including 456 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 0.070 (456 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBN	NM_002485.5	c.1845+419A>G		intron_variant	Intron 11 of 15	ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.1845+419A>G		intron_variant	Intron 11 of 15	1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10682 AN: 152074 Hom.: 455 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0701 AC: 10676 AN: 152192 Hom.: 456 Cov.: 32 AF XY: 0.0714 AC XY: 5313 AN XY: 74380

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0777 Hom.: 708

Bravo AF: 0.0657

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.060
DANN	Benign	0.75

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: rs1805812; hg19: chr8-90965053;