Variant rs1805826 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002485.5(NBN):c.896+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,508,190 control chromosomes in the GnomAD database, including 2,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 273 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2535 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.364

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 8-89970328-C-T is Benign according to our data. Variant chr8-89970328-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1243368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBN	NM_002485.5 linkuse as main transcript	c.896+36G>A		intron_variant		ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8 linkuse as main transcript	c.896+36G>A		intron_variant		1	NM_002485.5	ENSP00000265433	P1

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6473

AN:

151448

Hom.:

272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0734

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0304

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0712

AC:

17475

AN:

245514

Hom.:

1222

AF XY:

0.0658

AC XY:

8756

AN XY:

133030

show subpopulations

Gnomad AFR exome

AF:

0.00955

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.181

Gnomad SAS exome

AF:

0.0682

Gnomad FIN exome

AF:

0.0764

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0573

GnomAD4 exome

AF:

0.0427

AC:

57907

AN:

1356624

Hom.:

2535

Cov.:

AF XY:

0.0428

AC XY:

29153

AN XY:

680462

show subpopulations

Gnomad4 AFR exome

AF:

0.00826

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.0682

Gnomad4 FIN exome

AF:

0.0722

Gnomad4 NFE exome

AF:

0.0290

Gnomad4 OTH exome

AF:

0.0430

GnomAD4 genome

AF:

0.0428

AC:

6480

AN:

151566

Hom.:

273

Cov.:

AF XY:

0.0479

AC XY:

3553

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.0739

Gnomad4 FIN

AF:

0.0779

Gnomad4 NFE

AF:

0.0304

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0465

Asia WGS

AF:

0.137

AC:

473

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Hereditary breast ovarian cancer syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over