rs2053071

chr19-38900291-C-Gchr19-38900291-C-T

Variant summary

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

The NM_002503.5(NFKBIB):c.179+80C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,409,268 control chromosomes in the GnomAD database, including 102,496 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 0.32 (9882 hom., cov: 32)
  • Exomes 𝑓: 0.38 (92614 hom.)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIB	NM_002503.5	c.179+80C>G		intron_variant		ENST00000313582.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIB	ENST00000313582.6	c.179+80C>G		intron_variant		1	NM_002503.5	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49235 AN: 151996 Hom.: 9872 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.378 AC: 475175 AN: 1257154 Hom.: 92614 AF XY: 0.381 AC XY: 233675 AN XY: 613682

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.324 AC: 49249 AN: 152114 Hom.: 9882 Cov.: 32 AF XY: 0.336 AC XY: 24965 AN XY: 74352

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.346

Alfa AF: 0.334 Hom.: 1337

Bravo AF: 0.317

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.7
Dann	Benign	0.75

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: rs2053071; hg19: chr19-39390931; COSMIC: COSV50878134; COSMIC: COSV50878134;