NM_002485.5:c.942G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_002485.5(NBN):c.942G>A(p.Val314Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,632 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V314V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NBN
NM_002485.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.33

Publications

0 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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 8-89964462-C-T is Benign according to our data. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89964462-C-T is described in CliVar as Likely_benign. Clinvar id is 232196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBN	NM_002485.5 link	c.942G>A	p.Val314Val	synonymous_variant	Exon 8 of 16	ENST00000265433.8	NP_002476.2	O60934

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8 link	c.942G>A	p.Val314Val	synonymous_variant	Exon 8 of 16	1	NM_002485.5	ENSP00000265433.4		O60934

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251238

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460632

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110984

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 20, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NBN: BP4, BP7 -

Hereditary cancer-predisposing syndrome

Benign:2

Mar 14, 2021

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jun 04, 2015

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Microcephaly, normal intelligence and immunodeficiency

Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.49

CADD

Benign

3.7

(source)

DANN

Benign

0.57

PhyloP100

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over