rs3736640

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.2071-61A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,486,034 control chromosomes in the GnomAD database, including 1,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 188 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1145 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.777

Publications

7 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), 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

NBN links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002485.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.97).

BP6

Variant 8-89943427-T-A is Benign according to our data. Variant chr8-89943427-T-A is described in ClinVar as Benign. ClinVar VariationId is 1226117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0906 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.2071-61A>T	intron	N/A	NP_002476.2
NBN	NM_001024688.3		c.1825-61A>T	intron	N/A	NP_001019859.1	A0A0C4DG07
NBN	NM_001440379.1		c.1825-61A>T	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.2071-61A>T	intron	N/A	ENSP00000265433.4	O60934
NBN	ENST00000697309.1		c.2071-61A>T	intron	N/A	ENSP00000513244.1	A0A8V8TKY5
NBN	ENST00000697293.1		c.2071-61A>T	intron	N/A	ENSP00000513230.1	A0A8V8TM80

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6325

AN:

152136

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.0543

Gnomad SAS

AF:

0.0971

Gnomad FIN

AF:

0.00980

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0492

GnomAD4 exome

AF:

0.0361

AC:

48188

AN:

1333780

Hom.:

1145

Cov.:

AF XY:

0.0379

AC XY:

25380

AN XY:

669778

show subpopulations

African (AFR)

AF:

0.0589

AC:

1786

AN:

30348

American (AMR)

AF:

0.0505

AC:

2214

AN:

43874

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

1035

AN:

25280

East Asian (EAS)

AF:

0.0669

AC:

2589

AN:

38700

South Asian (SAS)

AF:

0.0913

AC:

7584

AN:

83072

European-Finnish (FIN)

AF:

0.00848

AC:

415

AN:

48920

Middle Eastern (MID)

AF:

0.0408

AC:

222

AN:

5442

European-Non Finnish (NFE)

AF:

0.0301

AC:

30132

AN:

1002050

Other (OTH)

AF:

0.0394

AC:

2211

AN:

56094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2110

4219

6329

8438

10548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1220

2440

3660

4880

6100

<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:

0.0417

AC:

6346

AN:

152254

Hom.:

188

Cov.:

AF XY:

0.0410

AC XY:

3051

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0605

AC:

2512

AN:

41540

American (AMR)

AF:

0.0508

AC:

777

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0372

AC:

129

AN:

3468

East Asian (EAS)

AF:

0.0540

AC:

280

AN:

5182

South Asian (SAS)

AF:

0.0978

AC:

472

AN:

4824

European-Finnish (FIN)

AF:

0.00980

AC:

104

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0285

AC:

1939

AN:

68008

Other (OTH)

AF:

0.0553

AC:

117

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

286

573

859

1146

1432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0352

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.101

AC:

353

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0060

(source)

DANN

Benign

0.42

PhyloP100

-0.78

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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