rs1805826

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 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

NBN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
NBN	NM_002485.5 link	c.896+36G>A		intron_variant	Intron 7 of 15	ENST00000265433.8	NP_002476.2	O60934

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8 link	c.896+36G>A		intron_variant	Intron 7 of 15	1	NM_002485.5	ENSP00000265433.4		O60934

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

GnomAD2 exomes

AF:

0.0712

AC:

17475

AN:

245514

AF XY:

0.0658

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 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

African (AFR)

AF:

0.00826

AC:

258

AN:

31244

American (AMR)

AF:

0.184

AC:

8128

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.0194

AC:

494

AN:

25438

East Asian (EAS)

AF:

0.193

AC:

7547

AN:

39090

South Asian (SAS)

AF:

0.0682

AC:

5682

AN:

83280

European-Finnish (FIN)

AF:

0.0722

AC:

3712

AN:

51402

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

0.0290

AC:

29542

AN:

1019600

Other (OTH)

AF:

0.0430

AC:

2451

AN:

56998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2628

5256

7884

10512

13140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1248

2496

3744

4992

6240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0428

AC:

6480

AN:

151566

Hom.:

273

Cov.:

AF XY:

0.0479

AC XY:

3553

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.0101

AC:

412

AN:

40870

American (AMR)

AF:

0.110

AC:

1689

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3470

East Asian (EAS)

AF:

0.187

AC:

968

AN:

5178

South Asian (SAS)

AF:

0.0739

AC:

357

AN:

4830

European-Finnish (FIN)

AF:

0.0779

AC:

826

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0304

AC:

2068

AN:

68006

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

309

619

928

1238

1547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0339

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Apr 19, 2022

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.50

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over