chr19-38908009-T-C

Variant names:

• chr19-38908009-T-C
• rs3136645
• ENST00000572515.5:c.*302T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369699.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	NM_002503.5	MANE Select	c.969+350T>C		intron	N/A	NP_002494.2
	NFKBIB	NM_001369699.1		c.*302T>C		3_prime_UTR	Exon 5 of 5	NP_001356628.1
	NFKBIB	NM_001243116.2		c.711+350T>C		intron	N/A	NP_001230045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	ENST00000572515.5	TSL:1	c.*302T>C		3_prime_UTR	Exon 5 of 5	ENSP00000459728.1
	NFKBIB	ENST00000313582.6	TSL:1 MANE Select	c.969+350T>C		intron	N/A	ENSP00000312988.5
	NFKBIB	ENST00000392079.7	TSL:5	c.711+350T>C		intron	N/A	ENSP00000375929.4

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

African (AFR) AF: 0.313 AC: 6543 AN: 20920

American (AMR) AF: 0.360 AC: 2520 AN: 7008

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 2271 AN: 10128

East Asian (EAS) AF: 0.481 AC: 6490 AN: 13506

South Asian (SAS) AF: 0.170 AC: 4963 AN: 29254

European-Finnish (FIN) AF: 0.228 AC: 1973 AN: 8648

Middle Eastern (MID) AF: 0.189 AC: 438 AN: 2312

European-Non Finnish (NFE) AF: 0.167 AC: 142213 AN: 852058

Other (OTH) AF: 0.204 AC: 7424 AN: 36394

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

African (AFR) AF: 0.301 AC: 12461 AN: 41400

American (AMR) AF: 0.361 AC: 5519 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2436 AN: 5164

South Asian (SAS) AF: 0.176 AC: 846 AN: 4810

European-Finnish (FIN) AF: 0.254 AC: 2687 AN: 10578

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

European-Non Finnish (NFE) AF: 0.180 AC: 12243 AN: 67960

Other (OTH) AF: 0.237 AC: 496 AN: 2096

Alfa AF: 0.205 Hom.: 13844

Bravo AF: 0.262

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.44
PhyloP100		-1.1
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: rs3136645; hg19: chr19-39398649;