rs1805787

Variant names:

• chr8-89956075-C-G
• rs1805787
• NM_002485.5:c.1125-520G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-89956075-C-G
• chr8-89956075-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002485.5(NBN):​c.1125-520G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,248 control chromosomes in the GnomAD database, including 4,157 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 0.20 (4157 hom., cov: 31)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBN	NM_002485.5	c.1125-520G>C		intron_variant	Intron 9 of 15	ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.1125-520G>C		intron_variant	Intron 9 of 15	1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30503 AN: 151136 Hom.: 4160 Cov.: 31

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00465

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.202 AC: 30488 AN: 151248 Hom.: 4157 Cov.: 31 AF XY: 0.195 AC XY: 14380 AN XY: 73846

African (AFR) AF: 0.0539 AC: 2224 AN: 41296

American (AMR) AF: 0.156 AC: 2362 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3470

East Asian (EAS) AF: 0.00447 AC: 23 AN: 5150

South Asian (SAS) AF: 0.170 AC: 817 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2309 AN: 10228

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

European-Non Finnish (NFE) AF: 0.315 AC: 21331 AN: 67798

Other (OTH) AF: 0.190 AC: 400 AN: 2102

Alfa AF: 0.157 Hom.: 346

Bravo AF: 0.190

Asia WGS AF: 0.0690 AC: 238 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.72
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1805787; hg19: chr8-90968303;