rs3136645

Positions:

• chr19-38908009-T-C

Variant summary

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

The NM_001369699.1(NFKBIB):​c.*302T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,132,180 control chromosomes in the GnomAD database, including 22,082 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 0.25 (5217 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16865 hom.)
• Consequence: NFKBIB NM_001369699.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

NFKBIB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIB	NM_002503.5	c.969+350T>C		intron_variant		ENST00000313582.6	NP_002494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIB	ENST00000313582.6	c.969+350T>C		intron_variant		1	NM_002503.5	ENSP00000312988.5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37645 AN: 151832 Hom.: 5210 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.178 AC: 174835 AN: 980228 Hom.: 16865 Cov.: 31 AF XY: 0.178 AC XY: 81809 AN XY: 460334

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.248 AC: 37676 AN: 151952 Hom.: 5217 Cov.: 32 AF XY: 0.256 AC XY: 19055 AN XY: 74290

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.237

Alfa AF: 0.200 Hom.: 5860

Bravo AF: 0.262

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.44

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: rs3136645; hg19: chr19-39398649;