10-102397970-C-T

Position:

• chr10-102397970-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001322934.2(NFKB2):​c.662-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,613,662 control chromosomes in the GnomAD database, including 762,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66287 hom., cov: 32)
  • Exomes 𝑓: 0.98 (695977 hom.)
• Consequence: NFKB2 NM_001322934.2 intron
• Scores: Splicing: ADA: 0.00009998
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0320

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 10-102397970-C-T is Benign according to our data. Variant chr10-102397970-C-T is described in ClinVar as [Benign]. Clinvar id is 403232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102397970-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.662-11C>T		intron_variant		ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.662-11C>T		intron_variant			NM_001322934.2	ENSP00000499294.1

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141405 AN: 152138 Hom.: 66245 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.942

GnomAD3 exomes AF: 0.968 AC: 241521 AN: 249528 Hom.: 117216 AF XY: 0.970 AC XY: 131337 AN XY: 135390

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.980

Gnomad ASJ exome AF: 0.964

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.966

Gnomad FIN exome AF: 0.997

Gnomad NFE exome AF: 0.979

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.975 AC: 1425421 AN: 1461406 Hom.: 695977 Cov.: 38 AF XY: 0.975 AC XY: 709223 AN XY: 727052

Gnomad4 AFR exome AF: 0.786

Gnomad4 AMR exome AF: 0.979

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.968

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 0.981

Gnomad4 OTH exome AF: 0.965

GnomAD4 genome AF: 0.929 AC: 141504 AN: 152256 Hom.: 66287 Cov.: 32 AF XY: 0.932 AC XY: 69420 AN XY: 74450

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.964

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.943

Alfa AF: 0.966 Hom.: 74232

Bravo AF: 0.922

Asia WGS AF: 0.976 AC: 3393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Immunodeficiency, common variable, 10 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

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	-0.65
CADD	Benign	14
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0040
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: rs4919632; hg19: chr10-104157727;