rs11574851

chr10-102401202-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001322934.2(NFKB2):c.2094C>T(p.Asn698=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,595,236 control chromosomes in the GnomAD database, including 2,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (152 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2035 hom.)
• Consequence: NFKB2 NM_001322934.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.82

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-102401202-C-T is Benign according to our data. Variant chr10-102401202-C-T is described in ClinVar as [Benign]. Clinvar id is 474781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2	c.2094C>T	p.Asn698=	synonymous_variant	19/23	ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1	c.2094C>T	p.Asn698=	synonymous_variant	19/23		NM_001322934.2	P5

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5750 AN: 152102 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.00954

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0485

GnomAD3 exomes AF: 0.0426 AC: 10063 AN: 236134 Hom.: 247 AF XY: 0.0439 AC XY: 5615 AN XY: 127884

Gnomad AFR exome AF: 0.00841

Gnomad AMR exome AF: 0.0259

Gnomad ASJ exome AF: 0.0416

Gnomad EAS exome AF: 0.0535

Gnomad SAS exome AF: 0.0398

Gnomad FIN exome AF: 0.0485

Gnomad NFE exome AF: 0.0501

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0514 AC: 74232 AN: 1443016 Hom.: 2035 Cov.: 37 AF XY: 0.0511 AC XY: 36599 AN XY: 715644

Gnomad4 AFR exome AF: 0.00844

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0398

Gnomad4 EAS exome AF: 0.0814

Gnomad4 SAS exome AF: 0.0409

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.0539

Gnomad4 OTH exome AF: 0.0486

GnomAD4 genome AF: 0.0378 AC: 5750 AN: 152220 Hom.: 152 Cov.: 32 AF XY: 0.0378 AC XY: 2811 AN XY: 74422

Gnomad4 AFR AF: 0.00951

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.0649

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0508

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.0508

Alfa AF: 0.0486 Hom.: 251

Bravo AF: 0.0357

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency, common variable, 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.15
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs11574851; hg19: chr10-104160959; COSMIC: COSV50046518; COSMIC: COSV50046518;