rs1805818

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.1124+91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,425,474 control chromosomes in the GnomAD database, including 79,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8375 hom., cov: 32)

Exomes 𝑓: 0.33 ( 71311 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.128

Publications

15 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: 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

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=-0.77).

BP6

Variant 8-89958634-G-T is Benign according to our data. Variant chr8-89958634-G-T is described in ClinVar as Benign. ClinVar VariationId is 1177038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002485.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBN	NM_002485.5	MANE Select	c.1124+91C>A	intron	N/A	NP_002476.2
NBN	NM_001024688.3		c.878+91C>A	intron	N/A	NP_001019859.1	A0A0C4DG07
NBN	NM_001440379.1		c.878+91C>A	intron	N/A	NP_001427308.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBN	ENST00000265433.8	TSL:1 MANE Select	c.1124+91C>A	intron	N/A	ENSP00000265433.4	O60934
NBN	ENST00000697309.1		c.1124+91C>A	intron	N/A	ENSP00000513244.1	A0A8V8TKY5
NBN	ENST00000697293.1		c.1124+91C>A	intron	N/A	ENSP00000513230.1	A0A8V8TM80

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50201

AN:

151874

Hom.:

8366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.331

AC:

421396

AN:

1273482

Hom.:

71311

AF XY:

0.334

AC XY:

214041

AN XY:

641434

show subpopulations

African (AFR)

AF:

0.304

AC:

8775

AN:

28880

American (AMR)

AF:

0.355

AC:

15460

AN:

43492

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

7872

AN:

24904

East Asian (EAS)

AF:

0.477

AC:

17737

AN:

37152

South Asian (SAS)

AF:

0.426

AC:

34382

AN:

80720

European-Finnish (FIN)

AF:

0.358

AC:

17200

AN:

48022

Middle Eastern (MID)

AF:

0.338

AC:

1492

AN:

4412

European-Non Finnish (NFE)

AF:

0.315

AC:

300240

AN:

952138

Other (OTH)

AF:

0.339

AC:

18238

AN:

53762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12797

25594

38392

51189

63986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9302

18604

27906

37208

46510

<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:

0.331

AC:

50235

AN:

151992

Hom.:

8375

Cov.:

AF XY:

0.335

AC XY:

24896

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.307

AC:

12715

AN:

41458

American (AMR)

AF:

0.350

AC:

5354

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1091

AN:

3468

East Asian (EAS)

AF:

0.451

AC:

2327

AN:

5156

South Asian (SAS)

AF:

0.437

AC:

2100

AN:

4808

European-Finnish (FIN)

AF:

0.352

AC:

3706

AN:

10540

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.322

AC:

21886

AN:

67968

Other (OTH)

AF:

0.345

AC:

728

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1763

3526

5289

7052

8815

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:

0.320

Hom.:

21227

Bravo

AF:

0.326

Asia WGS

AF:

0.425

AC:

1479

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Microcephaly, normal intelligence and immunodeficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.2

(source)

DANN

Benign

0.78

PhyloP100

0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over