Variant rs1805786 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 NM_002485.5(NBN):c.1125-79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,428,956 control chromosomes in the GnomAD database, including 81,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8373 hom., cov: 32)

Exomes 𝑓: 0.34 ( 73340 hom. )

Consequence

NBN
NM_002485.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.645

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=-0.83).

BP6

Variant 8-89955634-G-T is Benign according to our data. Variant chr8-89955634-G-T is described in ClinVar as [Benign]. Clinvar id is 1239473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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.1125-79C>A		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8 linkuse as main transcript	c.1125-79C>A		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50199

AN:

151750

Hom.:

8364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.336

AC:

428632

AN:

1277088

Hom.:

73340

AF XY:

0.338

AC XY:

215756

AN XY:

639170

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.331

AC:

50233

AN:

151868

Hom.:

8373

Cov.:

AF XY:

0.336

AC XY:

24895

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.343

Alfa

AF:

0.334

Hom.:

1088

Bravo

AF:

0.326

Asia WGS

AF:

0.425

AC:

1478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.6

DANN

Benign

0.29

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