rs3736639

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2071-30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,586,096 control chromosomes in the GnomAD database, including 90,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8517 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81965 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.723

Publications

14 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=-0.9).

BP6

Variant 8-89943396-T-A is Benign according to our data. Variant chr8-89943396-T-A is described in ClinVar as Benign. ClinVar VariationId is 258769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBN	NM_002485.5 link	c.2071-30A>T		intron_variant	Intron 13 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.2071-30A>T		intron_variant	Intron 13 of 15	1	NM_002485.5	ENSP00000265433.4		O60934

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50662

AN:

151826

Hom.:

8507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.342

GnomAD2 exomes

AF:

0.354

AC:

88533

AN:

250182

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.335

AC:

479781

AN:

1434152

Hom.:

81965

Cov.:

AF XY:

0.337

AC XY:

241007

AN XY:

715146

show subpopulations

African (AFR)

AF:

0.317

AC:

10344

AN:

32642

American (AMR)

AF:

0.359

AC:

15992

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8244

AN:

25944

East Asian (EAS)

AF:

0.479

AC:

18885

AN:

39446

South Asian (SAS)

AF:

0.429

AC:

36708

AN:

85620

European-Finnish (FIN)

AF:

0.362

AC:

19087

AN:

52734

Middle Eastern (MID)

AF:

0.342

AC:

1951

AN:

5708

European-Non Finnish (NFE)

AF:

0.320

AC:

348163

AN:

1087938

Other (OTH)

AF:

0.343

AC:

20407

AN:

59520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

15025

30050

45074

60099

75124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11316

22632

33948

45264

56580

<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:

0.334

AC:

50708

AN:

151944

Hom.:

8517

Cov.:

AF XY:

0.339

AC XY:

25150

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.317

AC:

13126

AN:

41438

American (AMR)

AF:

0.353

AC:

5379

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1091

AN:

3468

East Asian (EAS)

AF:

0.450

AC:

2327

AN:

5166

South Asian (SAS)

AF:

0.438

AC:

2108

AN:

4818

European-Finnish (FIN)

AF:

0.354

AC:

3728

AN:

10530

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21889

AN:

67954

Other (OTH)

AF:

0.347

AC:

732

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1744

3487

5231

6974

8718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.332

Hom.:

1591

Bravo

AF:

0.330

Asia WGS

AF:

0.426

AC:

1481

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Microcephaly, normal intelligence and immunodeficiency

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Acute lymphoid leukemia

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

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

Significance: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

-0.90

CADD

Benign

0.65

(source)

DANN

Benign

0.38

PhyloP100

-0.72

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