chr10-102399939-G-A

Variant names:

• chr10-102399939-G-A
• rs11574849
• NM_001322934.2:c.1470-141G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322934.2(NFKB2):​c.1470-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,069,208 control chromosomes in the GnomAD database, including 2,463 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 0.081 (598 hom., cov: 32)
  • Exomes 𝑓: 0.058 (1865 hom.)
• Consequence: NFKB2 NM_001322934.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 23 publications found

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]

NFKB2 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• deficiency in anterior pituitary function - variable immunodeficiency syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.1470-141G>A		intron_variant	Intron 14 of 22	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.1470-141G>A		intron_variant	Intron 14 of 22		NM_001322934.2	ENSP00000499294.1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12386 AN: 152140 Hom.: 596 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0576 AC: 52837 AN: 916950 Hom.: 1865 Cov.: 12 AF XY: 0.0569 AC XY: 26349 AN XY: 462926

African (AFR) AF: 0.141 AC: 3080 AN: 21786

American (AMR) AF: 0.0389 AC: 1113 AN: 28624

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 1774 AN: 18310

East Asian (EAS) AF: 0.000180 AC: 6 AN: 33384

South Asian (SAS) AF: 0.0328 AC: 2068 AN: 63086

European-Finnish (FIN) AF: 0.0521 AC: 1811 AN: 34776

Middle Eastern (MID) AF: 0.0818 AC: 377 AN: 4610

European-Non Finnish (NFE) AF: 0.0593 AC: 39739 AN: 670642

Other (OTH) AF: 0.0687 AC: 2869 AN: 41732

GnomAD4 genome AF: 0.0815 AC: 12403 AN: 152258 Hom.: 598 Cov.: 32 AF XY: 0.0788 AC XY: 5869 AN XY: 74450

African (AFR) AF: 0.140 AC: 5803 AN: 41528

American (AMR) AF: 0.0572 AC: 876 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 335 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.0565 AC: 600 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4366 AN: 68012

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0688 Hom.: 736

Bravo AF: 0.0835

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11574849; hg19: chr10-104159696;