19-38901177-T-C

Variant names:

• chr19-38901177-T-C
• rs12979755
• NM_002503.5:c.179+966T>C

Variant summary

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

The NM_002503.5(NFKBIB):​c.179+966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,070 control chromosomes in the GnomAD database, including 29,539 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 0.61 (29539 hom., cov: 33)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.179+966T>C		intron	N/A	NP_002494.2
	NFKBIB	NM_001369699.1		c.179+966T>C		intron	N/A	NP_001356628.1
	NFKBIB	NM_001243116.2		c.-80+1438T>C		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.179+966T>C		intron	N/A	ENSP00000312988.5
	NFKBIB	ENST00000572515.5	TSL:1	c.179+966T>C		intron	N/A	ENSP00000459728.1
	NFKBIB	ENST00000392079.7	TSL:5	c.-80+1438T>C		intron	N/A	ENSP00000375929.4

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93454 AN: 151952 Hom.: 29526 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.615 AC: 93501 AN: 152070 Hom.: 29539 Cov.: 33 AF XY: 0.627 AC XY: 46623 AN XY: 74334

African (AFR) AF: 0.499 AC: 20664 AN: 41442

American (AMR) AF: 0.724 AC: 11071 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4997 AN: 5184

South Asian (SAS) AF: 0.741 AC: 3571 AN: 4816

European-Finnish (FIN) AF: 0.707 AC: 7475 AN: 10574

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41498 AN: 67978

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.613 Hom.: 11069

Bravo AF: 0.611

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.72
PhyloP100		0.55
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: rs12979755; hg19: chr19-39391817;