rs2097825

Variant names:

• chr8-89998845-C-G
• rs2097825
• ENST00000396252.6:n.-230+4267G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-89998845-C-G
• chr8-89998845-C-T

Variant summary

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

The ENST00000756462.1(ENSG00000298563):​n.218+3378G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 150,602 control chromosomes in the GnomAD database, including 12,721 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 0.40 (12721 hom., cov: 29)
• Consequence: ENSG00000298563 ENST00000756462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• 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: Labcorp Genetics (formerly Invitae), Myriad Women's Health, G2P, Orphanet, ClinGen
• 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

ENSG00000298563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000756462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBN	ENST00000396252.6	TSL:5	n.-230+4267G>C		intron	N/A	ENSP00000379551.2	E2QRP0
	ENSG00000298563	ENST00000756462.1		n.218+3378G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60393 AN: 150500 Hom.: 12697 Cov.: 29

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.402 AC: 60472 AN: 150602 Hom.: 12721 Cov.: 29 AF XY: 0.404 AC XY: 29691 AN XY: 73466

African (AFR) AF: 0.541 AC: 22107 AN: 40874

American (AMR) AF: 0.379 AC: 5740 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2355 AN: 5114

South Asian (SAS) AF: 0.448 AC: 2144 AN: 4786

European-Finnish (FIN) AF: 0.349 AC: 3532 AN: 10120

Middle Eastern (MID) AF: 0.315 AC: 90 AN: 286

European-Non Finnish (NFE) AF: 0.328 AC: 22219 AN: 67812

Other (OTH) AF: 0.417 AC: 874 AN: 2096

Alfa AF: 0.365 Hom.: 1290

Bravo AF: 0.408

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.55
PhyloP100		-2.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2097825;

hg19: chr8-91011073;