Variant 8-89933828-A-G 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.*1754T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 232,162 control chromosomes in the GnomAD database, including 12,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7671 hom., cov: 31)

Exomes 𝑓: 0.33 ( 4425 hom. )

Consequence

NBN
NM_002485.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.468

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 8-89933828-A-G is Benign according to our data. Variant chr8-89933828-A-G is described in ClinVar as [Benign]. Clinvar id is 363896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.*1754T>C		3_prime_UTR_variant	16/16	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.*1754T>C		3_prime_UTR_variant	16/16	1	NM_002485.5	ENSP00000265433	P1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48195

AN:

151926

Hom.:

7661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.332

AC:

26633

AN:

80122

Hom.:

4425

Cov.:

AF XY:

0.332

AC XY:

12251

AN XY:

36874

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.317

AC:

48232

AN:

152040

Hom.:

7671

Cov.:

AF XY:

0.316

AC XY:

23503

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.321

Hom.:

7700

Bravo

AF:

0.312

Asia WGS

AF:

0.309

AC:

1075

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly, normal intelligence and immunodeficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.0

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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