10-102395637-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000369966.8(NFKB2):c.-72-251C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 478,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: NFKB2 ENST00000369966.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 10-102395637-C-A is Benign according to our data. Variant chr10-102395637-C-A is described in ClinVar as [Benign]. Clinvar id is 2640790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0015 (228/152310) while in subpopulation NFE AF= 0.00275 (187/68000). AF 95% confidence interval is 0.00243. There are 0 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001077494.3	c.-72-251C>A		intron_variant
NFKB2	NM_001288724.1	c.-72-251C>A		intron_variant
NFKB2	NM_001322935.1	c.-72-251C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000369966.8	c.-72-251C>A		intron_variant		1		P5
NFKB2	ENST00000428099.6	c.-72-251C>A		intron_variant		1		A1
NFKB2	ENST00000601386.5	n.447-251C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 152192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00146 AC: 476 AN: 326652 Hom.: 0 AF XY: 0.00138 AC XY: 234 AN XY: 169636

Gnomad4 AFR exome AF: 0.000295

Gnomad4 AMR exome AF: 0.000641

Gnomad4 ASJ exome AF: 0.0000915

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000333

Gnomad4 FIN exome AF: 0.000302

Gnomad4 NFE exome AF: 0.00220

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.00150 AC: 228 AN: 152310 Hom.: 0 Cov.: 31 AF XY: 0.00161 AC XY: 120 AN XY: 74480

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000914

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

NFKB2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs574565770; hg19: chr10-104155394;