Variant rs13312970 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.2234+88C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,063,834 control chromosomes in the GnomAD database, including 1,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 433 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1188 hom. )

Consequence

NBN
ENST00000265433.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.771

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=-0.89).

BP6

Variant 8-89936938-G-C is Benign according to our data. Variant chr8-89936938-G-C is described in ClinVar as [Benign]. Clinvar id is 1232508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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.2234+88C>G		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.2234+88C>G		intron_variant		1	NM_002485.5	ENSP00000265433	P1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9124

AN:

152070

Hom.:

427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0577

Gnomad ASJ

AF:

0.0398

Gnomad EAS

AF:

0.0553

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0602

GnomAD4 exome

AF:

0.0415

AC:

37847

AN:

911646

Hom.:

1188

AF XY:

0.0432

AC XY:

20465

AN XY:

473746

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.0492

Gnomad4 ASJ exome

AF:

0.0433

Gnomad4 EAS exome

AF:

0.0689

Gnomad4 SAS exome

AF:

0.0938

Gnomad4 FIN exome

AF:

0.00825

Gnomad4 NFE exome

AF:

0.0323

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0601

AC:

9147

AN:

152188

Hom.:

433

Cov.:

AF XY:

0.0593

AC XY:

4416

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0577

Gnomad4 ASJ

AF:

0.0398

Gnomad4 EAS

AF:

0.0556

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.0298

Gnomad4 OTH

AF:

0.0667

Alfa

AF:

0.0455

Hom.:

Bravo

AF:

0.0652

Asia WGS

AF:

0.109

AC:

383

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.89

CADD

Benign

3.9

DANN

Benign

0.44

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