19-38904275-C-T

Variant names:

• chr19-38904275-C-T
• rs8108039
• NM_002503.5:c.180-740C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002503.5(NFKBIB):​c.180-740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,910 control chromosomes in the GnomAD database, including 2,739 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 0.18 (2739 hom., cov: 31)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	NM_002503.5	MANE Select	c.180-740C>T		intron	N/A	NP_002494.2
	NFKBIB	NM_001369699.1		c.180-740C>T		intron	N/A	NP_001356628.1
	NFKBIB	NM_001243116.2		c.-79-740C>T		intron	N/A	NP_001230045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	ENST00000313582.6	TSL:1 MANE Select	c.180-740C>T		intron	N/A	ENSP00000312988.5
	NFKBIB	ENST00000572515.5	TSL:1	c.180-740C>T		intron	N/A	ENSP00000459728.1
	NFKBIB	ENST00000392079.7	TSL:5	c.-79-740C>T		intron	N/A	ENSP00000375929.4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27880 AN: 151790 Hom.: 2741 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.184 AC: 27881 AN: 151910 Hom.: 2739 Cov.: 31 AF XY: 0.187 AC XY: 13907 AN XY: 74218

African (AFR) AF: 0.140 AC: 5808 AN: 41424

American (AMR) AF: 0.157 AC: 2390 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1892 AN: 5150

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2289 AN: 10518

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13198 AN: 67956

Other (OTH) AF: 0.183 AC: 386 AN: 2106

Alfa AF: 0.144 Hom.: 462

Bravo AF: 0.178

Asia WGS AF: 0.247 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8108039; hg19: chr19-39394915;