rs12772374

chr10-102397154-A-G

Variant summary

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

The NM_001322934.2(NFKB2):c.395+99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,559,794 control chromosomes in the GnomAD database, including 22,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1605 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20625 hom.)
• Consequence: NFKB2 NM_001322934.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678

Genes affected

NFKB2 (HGNC:7795): (nuclear factor kappa B subunit 2) This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-102397154-A-G is Benign according to our data. Variant chr10-102397154-A-G is described in ClinVar as [Benign]. Clinvar id is 2628274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2	c.395+99A>G		intron_variant		ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1	c.395+99A>G		intron_variant			NM_001322934.2	P5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20096 AN: 152092 Hom.: 1610 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.166 AC: 234134 AN: 1407584 Hom.: 20625 Cov.: 30 AF XY: 0.164 AC XY: 113822 AN XY: 695118

Gnomad4 AFR exome AF: 0.0404

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.132 AC: 20096 AN: 152210 Hom.: 1605 Cov.: 32 AF XY: 0.132 AC XY: 9791 AN XY: 74408

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.134

Alfa AF: 0.159 Hom.: 270

Bravo AF: 0.122

Asia WGS AF: 0.114 AC: 394 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.1
Dann	Benign	0.39

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: rs12772374; hg19: chr10-104156911;