rs56230731

chr8-42316862-G-Achr8-42316862-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001556.3(IKBKB):c.1083G>A(p.Leu361=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0128 in 1,614,106 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (4 hom., cov: 32)
  • Exomes 𝑓: 0.013 (181 hom.)
• Consequence: IKBKB NM_001556.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.06

Genes affected

IKBKB (HGNC:5960): (inhibitor of nuclear factor kappa B kinase subunit beta) The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 8-42316862-G-A is Benign according to our data. Variant chr8-42316862-G-A is described in ClinVar as [Benign]. Clinvar id is 474788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00977 (1488/152284) while in subpopulation NFE AF= 0.0169 (1150/68030). AF 95% confidence interval is 0.0161. There are 4 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3	c.1083G>A	p.Leu361=	synonymous_variant	11/22	ENST00000520810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6	c.1083G>A	p.Leu361=	synonymous_variant	11/22	1	NM_001556.3	P1

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1488 AN: 152166 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00925 AC: 2323 AN: 251040 Hom.: 22 AF XY: 0.00885 AC XY: 1201 AN XY: 135742

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.00915

GnomAD4 exome AF: 0.0131 AC: 19185 AN: 1461822 Hom.: 181 Cov.: 31 AF XY: 0.0126 AC XY: 9176 AN XY: 727214

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.00985

GnomAD4 genome AF: 0.00977 AC: 1488 AN: 152284 Hom.: 4 Cov.: 32 AF XY: 0.00897 AC XY: 668 AN XY: 74458

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0124 Hom.: 10

Bravo AF: 0.00875

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe combined immunodeficiency due to IKK2 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	5.2
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs56230731; hg19: chr8-42174380;