8-89971157-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_002485.5(NBN):c.702+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,607,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.404

Publications

1 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 8-89971157-C-G is Benign according to our data. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89971157-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 234384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000657 (10/152228) while in subpopulation EAS AF = 0.00193 (10/5188). AF 95% confidence interval is 0.00105. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBN	NM_002485.5 link	c.702+16G>C		intron_variant	Intron 6 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.702+16G>C		intron_variant	Intron 6 of 15	1	NM_002485.5	ENSP00000265433.4		O60934

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000188

AC:

AN:

249498

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00251

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1455346

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

115

AN XY:

724194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33320

American (AMR)

AF:

0.00

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00550

AC:

217

AN:

39482

South Asian (SAS)

AF:

0.00

AC:

AN:

85978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107298

Other (OTH)

AF:

0.0000833

AC:

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000121

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 22, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Microcephaly, normal intelligence and immunodeficiency

Benign:1

Dec 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.57

CADD

Benign

9.4

(source)

DANN

Benign

0.81

PhyloP100

-0.40

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

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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