chr10-102397970-C-T

Variant names:

• chr10-102397970-C-T
• rs4919632
• NM_001322934.2:c.662-11C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• deficiency in anterior pituitary function - variable immunodeficiency syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 403232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKB2	NM_001322934.2	MANE Select	c.662-11C>T		intron	N/A	NP_001309863.1	Q00653-1
	NFKB2	NM_001077494.3		c.662-11C>T		intron	N/A	NP_001070962.1	Q00653-1
	NFKB2	NM_001261403.3		c.662-11C>T		intron	N/A	NP_001248332.1	Q00653-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKB2	ENST00000661543.1	MANE Select	c.662-11C>T		intron	N/A	ENSP00000499294.1	Q00653-1
	NFKB2	ENST00000369966.8	TSL:1	c.662-11C>T		intron	N/A	ENSP00000358983.3	Q00653-1
	NFKB2	ENST00000189444.11	TSL:1	c.662-11C>T		intron	N/A	ENSP00000189444.6	Q00653-4

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

GnomAD2 exomes AF: 0.968 AC: 241521 AN: 249528 AF XY: 0.970

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 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

African (AFR) AF: 0.786 AC: 26308 AN: 33468

American (AMR) AF: 0.979 AC: 43769 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 25186 AN: 26128

East Asian (EAS) AF: 1.00 AC: 39683 AN: 39698

South Asian (SAS) AF: 0.968 AC: 83487 AN: 86248

European-Finnish (FIN) AF: 0.996 AC: 53209 AN: 53408

Middle Eastern (MID) AF: 0.957 AC: 5515 AN: 5760

European-Non Finnish (NFE) AF: 0.981 AC: 1089981 AN: 1111602

Other (OTH) AF: 0.965 AC: 58283 AN: 60372

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

African (AFR) AF: 0.797 AC: 33071 AN: 41512

American (AMR) AF: 0.967 AC: 14802 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3348 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5188 AN: 5192

South Asian (SAS) AF: 0.970 AC: 4680 AN: 4824

European-Finnish (FIN) AF: 0.997 AC: 10590 AN: 10618

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.980 AC: 66661 AN: 68018

Other (OTH) AF: 0.943 AC: 1991 AN: 2112

Alfa AF: 0.959 Hom.: 94297

Bravo AF: 0.922

Asia WGS AF: 0.976 AC: 3393 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Immunodeficiency, common variable, 10 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4919632; hg19: chr10-104157727;