rs1805790

Variant names:

• chr8-89962473-T-C
• rs1805790
• NM_002485.5:c.994+1937A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-89962473-T-C
• chr8-89962473-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• idiopathic aplastic anemia

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NBN	NM_002485.5	c.994+1937A>G		intron_variant	Intron 8 of 15	ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.994+1937A>G		intron_variant	Intron 8 of 15	1	NM_002485.5	ENSP00000265433.4

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

African (AFR) AF: 0.230 AC: 9546 AN: 41506

American (AMR) AF: 0.341 AC: 5216 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5164

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4822

European-Finnish (FIN) AF: 0.353 AC: 3726 AN: 10558

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21852 AN: 67956

Other (OTH) AF: 0.326 AC: 686 AN: 2106

Alfa AF: 0.308 Hom.: 973

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
PhyloP100		-0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1805790; hg19: chr8-90974701;