rs11191279

chr10-102401464-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001322934.2(NFKB2):c.2239C>T(p.Leu747=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,894 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (13 hom., cov: 33)
  • Exomes 𝑓: 0.016 (238 hom.)
• Consequence: NFKB2 NM_001322934.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.896

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-102401464-C-T is Benign according to our data. Variant chr10-102401464-C-T is described in ClinVar as [Benign]. Clinvar id is 474782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.896 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00986 (1501/152234) while in subpopulation NFE AF= 0.0165 (1123/67994). AF 95% confidence interval is 0.0157. There are 13 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2	c.2239C>T	p.Leu747=	synonymous_variant	20/23	ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1	c.2239C>T	p.Leu747=	synonymous_variant	20/23		NM_001322934.2	P5

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152118 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.0106 AC: 2636 AN: 249040 Hom.: 29 AF XY: 0.0106 AC XY: 1438 AN XY: 135160

Gnomad AFR exome AF: 0.00362

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0155 AC: 22685 AN: 1461660 Hom.: 238 Cov.: 36 AF XY: 0.0150 AC XY: 10936 AN XY: 727140

Gnomad4 AFR exome AF: 0.00221

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00322

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00986 AC: 1501 AN: 152234 Hom.: 13 Cov.: 33 AF XY: 0.00935 AC XY: 696 AN XY: 74432

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00951

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.0148 Hom.: 18

Bravo AF: 0.00981

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 10 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 01, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.8
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11191279; hg19: chr10-104161221; COSMIC: COSV50068249; COSMIC: COSV50068249;