rs7011299

Variant names:

• chr8-90001011-C-G
• rs7011299
• ENST00000396252.6:n.-230+2101G>C

Variant summary

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

The ENST00000756462.1(ENSG00000298563):​n.218+1212G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,192 control chromosomes in the GnomAD database, including 7,514 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 (7514 hom., cov: 33)
• Consequence: ENSG00000298563 ENST00000756462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 5 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), G2P, Myriad Women's Health, ClinGen, Orphanet
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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+2101G>C		intron	N/A	ENSP00000379551.2	E2QRP0
	ENSG00000298563	ENST00000756462.1		n.218+1212G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47003 AN: 152074 Hom.: 7506 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.309 AC: 47031 AN: 152192 Hom.: 7514 Cov.: 33 AF XY: 0.315 AC XY: 23408 AN XY: 74428

African (AFR) AF: 0.231 AC: 9600 AN: 41526

American (AMR) AF: 0.341 AC: 5210 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3472

East Asian (EAS) AF: 0.453 AC: 2340 AN: 5168

South Asian (SAS) AF: 0.438 AC: 2116 AN: 4826

European-Finnish (FIN) AF: 0.354 AC: 3747 AN: 10584

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

European-Non Finnish (NFE) AF: 0.323 AC: 21945 AN: 68002

Other (OTH) AF: 0.329 AC: 695 AN: 2114

Alfa AF: 0.320 Hom.: 1003

Bravo AF: 0.301

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.41
PhyloP100		-0.33
PromoterAI		0.024	Neutral

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: rs7011299;

hg19: chr8-91013239;