8-42271987-A-T

Variant summary

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

The NM_001556.3(IKBKB):c.-18-96A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,257,516 control chromosomes in the GnomAD database, including 142,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13469 hom., cov: 33)
  • Exomes 𝑓: 0.48 (129374 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-42271987-A-T is Benign according to our data. Variant chr8-42271987-A-T is described in ClinVar as [Benign]. Clinvar id is 1266286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3	c.-18-96A>T		intron_variant		ENST00000520810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6	c.-18-96A>T		intron_variant		1	NM_001556.3	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59334 AN: 152056 Hom.: 13458 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.479 AC: 529792 AN: 1105342 Hom.: 129374 Cov.: 14 AF XY: 0.480 AC XY: 265237 AN XY: 552238

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.511

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.390 AC: 59355 AN: 152174 Hom.: 13469 Cov.: 33 AF XY: 0.393 AC XY: 29264 AN XY: 74384

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.415

Alfa AF: 0.321 Hom.: 1051

Bravo AF: 0.391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.046
Dann	Benign	0.52

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: rs3747811; hg19: chr8-42129505;