8-42271987-A-T

Variant names:

• chr8-42271987-A-T
• rs3747811
• NM_001556.3:c.-18-96A>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:3
• 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 rank	MANE	Protein	UniProt
IKBKB	NM_001556.3	c.-18-96A>T		intron_variant	Intron 1 of 21	ENST00000520810.6	NP_001547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKBKB	ENST00000520810.6	c.-18-96A>T		intron_variant	Intron 1 of 21	1	NM_001556.3	ENSP00000430684.1

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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;