Variant 10-102401464-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.896

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1501 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKB2	NM_001322934.2 linkuse as main transcript	c.2239C>T	p.Leu747=	synonymous_variant	20/23	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1 linkuse as main transcript	c.2239C>T	p.Leu747=	synonymous_variant	20/23		NM_001322934.2	ENSP00000499294	P5	Q00653-1

Frequencies

GnomAD3 genomes

AF:

0.00987

AC:

1502

AN:

152118

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0106

AC XY:

1438

AN XY:

135160

show subpopulations

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.:

AF XY:

0.0150

AC XY:

10936

AN XY:

727140

show subpopulations

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.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74432

show subpopulations

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.:

Bravo

AF:

0.00981

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0155

EpiControl

AF:

0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 10

Benign:2

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

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over