rs3136642

chr19-38907776-A-Gchr19-38907776-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572515.5(NFKBIB):c.*69A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,452,402 control chromosomes in the GnomAD database, including 115,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14549 hom., cov: 32)
  • Exomes 𝑓: 0.39 (101392 hom.)
• Consequence: NFKBIB ENST00000572515.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

Genes affected

NFKBIB (HGNC:7798): (NFKB inhibitor beta) The protein encoded by this gene belongs to the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B, which translocates to the nucleus to function as a transcription factor. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIB	NM_002503.5	c.969+117A>G		intron_variant		ENST00000313582.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIB	ENST00000572515.5	c.*69A>G		3_prime_UTR_variant	5/5	1
NFKBIB	ENST00000313582.6	c.969+117A>G		intron_variant		1	NM_002503.5	P1
NFKBIB	ENST00000392079.7	c.711+117A>G		intron_variant		5
NFKBIB	ENST00000509705.3	c.*832A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65185 AN: 151974 Hom.: 14541 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.389 AC: 505829 AN: 1300310 Hom.: 101392 Cov.: 34 AF XY: 0.388 AC XY: 244093 AN XY: 629336

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.429 AC: 65213 AN: 152092 Hom.: 14549 Cov.: 32 AF XY: 0.437 AC XY: 32473 AN XY: 74362

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.424

Alfa AF: 0.396 Hom.: 13157

Bravo AF: 0.443

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.13
Dann	Benign	0.65

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: rs3136642; hg19: chr19-39398416;