19-38906009-C-T

Variant names:

• chr19-38906009-C-T
• rs3136641
• NM_002503.5:c.619+474C>T

Variant summary

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

The NM_002503.5(NFKBIB):​c.619+474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,974 control chromosomes in the GnomAD database, including 3,695 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 0.21 (3695 hom., cov: 31)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIB	NM_002503.5	c.619+474C>T		intron_variant	Intron 3 of 5	ENST00000313582.6	NP_002494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIB	ENST00000313582.6	c.619+474C>T		intron_variant	Intron 3 of 5	1	NM_002503.5	ENSP00000312988.5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32434 AN: 151856 Hom.: 3697 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32431 AN: 151974 Hom.: 3695 Cov.: 31 AF XY: 0.216 AC XY: 16046 AN XY: 74288

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.218

Alfa AF: 0.229 Hom.: 5379

Bravo AF: 0.207

Asia WGS AF: 0.250 AC: 867 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	0.80
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3136641; hg19: chr19-39396649;