rs12772374

Variant names:

• chr10-102397154-A-G
• rs12772374
• NM_001322934.2:c.395+99A>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 rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.395+99A>G		intron_variant	Intron 6 of 22	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.395+99A>G		intron_variant	Intron 6 of 22		NM_001322934.2	ENSP00000499294.1

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

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;