chr8-89942942-G-C

Position:

• chr8-89942942-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002485.5(NBN):​c.2184+311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,670 control chromosomes in the GnomAD database, including 7,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7467 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.960

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-89942942-G-C is Benign according to our data. Variant chr8-89942942-G-C is described in ClinVar as [Benign]. Clinvar id is 1272514.Status of the report is criteria_provided_single_submitter, 1 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	Protein	UniProt
NBN	NM_002485.5	c.2184+311C>G		intron_variant		ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.2184+311C>G		intron_variant		1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46788 AN: 151570 Hom.: 7460 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46814 AN: 151670 Hom.: 7467 Cov.: 32 AF XY: 0.314 AC XY: 23283 AN XY: 74088

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.326

Alfa AF: 0.311 Hom.: 948

Bravo AF: 0.300

Asia WGS AF: 0.420 AC: 1459 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs6470523; hg19: chr8-90955170;