rs3026271

chr8-89971024-A-G

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.702+149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 728,674 control chromosomes in the GnomAD database, including 1,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (222 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1119 hom.)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-89971024-A-G is Benign according to our data. Variant chr8-89971024-A-G is described in ClinVar as [Benign]. Clinvar id is 1263646.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.702+149T>C		intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.702+149T>C		intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6575 AN: 152174 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0557 AC: 32123 AN: 576382 Hom.: 1119 AF XY: 0.0551 AC XY: 16667 AN XY: 302258

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0458

Gnomad4 EAS exome AF: 0.000170

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0470

Gnomad4 NFE exome AF: 0.0657

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.0431 AC: 6571 AN: 152292 Hom.: 222 Cov.: 32 AF XY: 0.0423 AC XY: 3147 AN XY: 74466

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0501 Hom.: 27

Bravo AF: 0.0409

Asia WGS AF: 0.0130 AC: 46 AN: 3478

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

Jun 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.6
Dann	Benign	0.32

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: rs3026271; hg19: chr8-90983252;