rs36226237

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000396252.6(NBN):n.-173+4_-173+7delAGTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 358,176 control chromosomes in the GnomAD database, including 327 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 125 hom., cov: 32)

Exomes 𝑓: 0.036 ( 202 hom. )

Consequence

NBN
ENST00000396252.6 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.178

Publications

4 publications found

Variant links:

Genes affected

ENSG00000309953 (HGNC:):

ENSG00000309953 links:

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 ENST00000396252.6, 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 -16 ACMG points.

BP6

Variant 8-89984909-ATACT-A is Benign according to our data. Variant chr8-89984909-ATACT-A is described in ClinVar as Benign. ClinVar VariationId is 1164691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396252.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBN	NM_002485.5	MANE Select	c.-352_-349delAGTA		upstream_gene	N/A	NP_002476.2
	NBN	NM_001024688.3		c.-648_-645delAGTA		upstream_gene	N/A	NP_001019859.1	A0A0C4DG07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000309953	ENST00000846143.1		n.585_588delTTAC	non_coding_transcript_exon	Exon 1 of 1
NBN	ENST00000396252.6	TSL:5	n.-173+4_-173+7delAGTA	splice_region intron	N/A	ENSP00000379551.2	E2QRP0
NBN	ENST00000265433.8	TSL:1 MANE Select	c.-352_-349delAGTA	upstream_gene	N/A	ENSP00000265433.4	O60934

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4913

AN:

152230

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00897

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.0206

GnomAD4 exome

AF:

0.0364

AC:

7482

AN:

205828

Hom.:

202

AF XY:

0.0363

AC XY:

3776

AN XY:

104062

show subpopulations

African (AFR)

AF:

0.00972

AC:

AN:

6278

American (AMR)

AF:

0.0150

AC:

105

AN:

7000

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

347

AN:

7978

East Asian (EAS)

AF:

0.00

AC:

AN:

16936

South Asian (SAS)

AF:

0.0118

AC:

155

AN:

13132

European-Finnish (FIN)

AF:

0.0336

AC:

399

AN:

11860

Middle Eastern (MID)

AF:

0.0209

AC:

AN:

1052

European-Non Finnish (NFE)

AF:

0.0464

AC:

5924

AN:

127690

Other (OTH)

AF:

0.0337

AC:

469

AN:

13902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

356

712

1067

1423

1779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0322

AC:

4912

AN:

152348

Hom.:

125

Cov.:

AF XY:

0.0299

AC XY:

2231

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00892

AC:

371

AN:

41588

American (AMR)

AF:

0.0196

AC:

300

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

169

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5192

South Asian (SAS)

AF:

0.0130

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0369

AC:

392

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0516

AC:

3511

AN:

68022

Other (OTH)

AF:

0.0204

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

232

465

697

930

1162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0447

Hom.:

Bravo

AF:

0.0306

Asia WGS

AF:

0.00606

AC:

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)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Splicing

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

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