rs3736639

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002485.5(NBN):c.2071-30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,586,096 control chromosomes in the GnomAD database, including 90,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8517 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81965 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.723

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-89943396-T-A is Benign according to our data. Variant chr8-89943396-T-A is described in ClinVar as [Benign]. Clinvar id is 258769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-89943396-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5 linkuse as main transcript	c.2071-30A>T		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8 linkuse as main transcript	c.2071-30A>T		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50662

AN:

151826

Hom.:

8507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.354

AC:

88533

AN:

250182

Hom.:

15857

AF XY:

0.356

AC XY:

48126

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.335

AC:

479781

AN:

1434152

Hom.:

81965

Cov.:

AF XY:

0.337

AC XY:

241007

AN XY:

715146

show subpopulations

Gnomad4 AFR exome

AF:

0.317

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.429

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.334

AC:

50708

AN:

151944

Hom.:

8517

Cov.:

AF XY:

0.339

AC XY:

25150

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.353

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.332

Hom.:

1591

Bravo

AF:

0.330

Asia WGS

AF:

0.426

AC:

1481

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Microcephaly, normal intelligence and immunodeficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Acute lymphoid leukemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.65

Dann

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over