rs6470522

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002485.5(NBN):​c.2184+1000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,164 control chromosomes in the GnomAD database, including 56,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 56656 hom., cov: 32)

Consequence

NBN
NM_002485.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.309
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBNNM_002485.5 linkuse as main transcriptc.2184+1000T>C intron_variant ENST00000265433.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBNENST00000265433.8 linkuse as main transcriptc.2184+1000T>C intron_variant 1 NM_002485.5 P1

Frequencies

GnomAD3 genomes
AF:
0.860
AC:
130762
AN:
152046
Hom.:
56592
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.949
Gnomad AMI
AF:
0.708
Gnomad AMR
AF:
0.832
Gnomad ASJ
AF:
0.828
Gnomad EAS
AF:
0.670
Gnomad SAS
AF:
0.827
Gnomad FIN
AF:
0.821
Gnomad MID
AF:
0.869
Gnomad NFE
AF:
0.839
Gnomad OTH
AF:
0.854
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.860
AC:
130883
AN:
152164
Hom.:
56656
Cov.:
32
AF XY:
0.858
AC XY:
63810
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.949
Gnomad4 AMR
AF:
0.833
Gnomad4 ASJ
AF:
0.828
Gnomad4 EAS
AF:
0.669
Gnomad4 SAS
AF:
0.827
Gnomad4 FIN
AF:
0.821
Gnomad4 NFE
AF:
0.839
Gnomad4 OTH
AF:
0.855
Alfa
AF:
0.837
Hom.:
104037
Bravo
AF:
0.863
Asia WGS
AF:
0.774
AC:
2690
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
2.1
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6470522; hg19: chr8-90954481; API