Variant rs3736640 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000265433.8(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
ENST00000265433.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.777

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=-0.97).

BP6

Variant 8-89943427-T-A is Benign according to our data. Variant chr8-89943427-T-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBN	NM_002485.5 linkuse as main transcript	c.2071-61A>T		intron_variant		ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8 linkuse as main transcript	c.2071-61A>T		intron_variant		1	NM_002485.5	ENSP00000265433	P1

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

Gnomad4 AFR exome

AF:

0.0589

Gnomad4 AMR exome

AF:

0.0505

Gnomad4 ASJ exome

AF:

0.0409

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.0913

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.0301

Gnomad4 OTH exome

AF:

0.0394

GnomAD4 genome

AF:

0.0417

AC:

6346

AN:

152254

Hom.:

188

Cov.:

AF XY:

0.0410

AC XY:

3051

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0605

Gnomad4 AMR

AF:

0.0508

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.0540

Gnomad4 SAS

AF:

0.0978

Gnomad4 FIN

AF:

0.00980

Gnomad4 NFE

AF:

0.0285

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0352

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.101

AC:

353

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.97

CADD

Benign

0.0060

DANN

Benign

0.42

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