19-38908637-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.970-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,442,270 control chromosomes in the GnomAD database, including 39,023 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 0.19 (3109 hom., cov: 30)
  • Exomes 𝑓: 0.23 (35914 hom.)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIB	NM_002503.5	c.970-94C>T		intron_variant		ENST00000313582.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIB	ENST00000313582.6	c.970-94C>T		intron_variant		1	NM_002503.5	P1
NFKBIB	ENST00000392079.7	c.712-94C>T		intron_variant		5
NFKBIB	ENST00000509705.3	c.*1693C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28083 AN: 151390 Hom.: 3110 Cov.: 30

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.232 AC: 299712 AN: 1290774 Hom.: 35914 Cov.: 35 AF XY: 0.235 AC XY: 147866 AN XY: 629072

Gnomad4 AFR exome AF: 0.0672

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.185 AC: 28084 AN: 151496 Hom.: 3109 Cov.: 30 AF XY: 0.184 AC XY: 13608 AN XY: 74006

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.204

Alfa AF: 0.225 Hom.: 2341

Bravo AF: 0.180

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3136646; hg19: chr19-39399277; COSMIC: COSV58005726; COSMIC: COSV58005726;