19-38907776-A-G

Variant names:

• chr19-38907776-A-G
• rs3136642
• ENST00000572515.5:c.*69A>G

Variant summary

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

The NM_001369699.1(NFKBIB):​c.*69A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,452,402 control chromosomes in the GnomAD database, including 115,941 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 0.43 (14549 hom., cov: 32)
  • Exomes 𝑓: 0.39 (101392 hom.)
• Consequence: NFKBIB NM_001369699.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 20 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 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+117A>G		intron	N/A	NP_002494.2
	NFKBIB	NM_001369699.1		c.*69A>G		3_prime_UTR	Exon 5 of 5	NP_001356628.1	Q15653-2
	NFKBIB	NM_001243116.2		c.711+117A>G		intron	N/A	NP_001230045.1	G5E9C2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	ENST00000572515.5	TSL:1	c.*69A>G		3_prime_UTR	Exon 5 of 5	ENSP00000459728.1	Q15653-2
	NFKBIB	ENST00000313582.6	TSL:1 MANE Select	c.969+117A>G		intron	N/A	ENSP00000312988.5	Q15653-1
	NFKBIB	ENST00000392079.7	TSL:5	c.711+117A>G		intron	N/A	ENSP00000375929.4	G5E9C2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65185 AN: 151974 Hom.: 14541 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.389 AC: 505829 AN: 1300310 Hom.: 101392 Cov.: 34 AF XY: 0.388 AC XY: 244093 AN XY: 629336

African (AFR) AF: 0.440 AC: 12533 AN: 28514

American (AMR) AF: 0.571 AC: 12651 AN: 22174

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 8711 AN: 19246

East Asian (EAS) AF: 0.710 AC: 24573 AN: 34606

South Asian (SAS) AF: 0.333 AC: 21499 AN: 64574

European-Finnish (FIN) AF: 0.434 AC: 19229 AN: 44310

Middle Eastern (MID) AF: 0.386 AC: 1694 AN: 4384

European-Non Finnish (NFE) AF: 0.373 AC: 383400 AN: 1028910

Other (OTH) AF: 0.402 AC: 21539 AN: 53592

GnomAD4 genome AF: 0.429 AC: 65213 AN: 152092 Hom.: 14549 Cov.: 32 AF XY: 0.437 AC XY: 32473 AN XY: 74362

African (AFR) AF: 0.438 AC: 18156 AN: 41482

American (AMR) AF: 0.551 AC: 8415 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1576 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3632 AN: 5162

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4826

European-Finnish (FIN) AF: 0.456 AC: 4831 AN: 10594

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25587 AN: 67974

Other (OTH) AF: 0.424 AC: 894 AN: 2108

Alfa AF: 0.398 Hom.: 19450

Bravo AF: 0.443

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-0.82
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: rs3136642; hg19: chr19-39398416;