19-38905695-A-T

Variant names:

• chr19-38905695-A-T
• rs2241704
• NM_002503.5:c.619+160A>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.619+160A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,114 control chromosomes in the GnomAD database, including 2,564 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 0.17 (2564 hom., cov: 32)
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIB	NM_002503.5	c.619+160A>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+160A>T		intron_variant	Intron 3 of 5	1	NM_002503.5	ENSP00000312988.5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25110 AN: 151996 Hom.: 2564 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.165 AC: 25105 AN: 152114 Hom.: 2564 Cov.: 32 AF XY: 0.166 AC XY: 12350 AN XY: 74360

African (AFR) AF: 0.0506 AC: 2101 AN: 41502

American (AMR) AF: 0.179 AC: 2738 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3470

East Asian (EAS) AF: 0.134 AC: 694 AN: 5166

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4818

European-Finnish (FIN) AF: 0.207 AC: 2193 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14464 AN: 67974

Other (OTH) AF: 0.176 AC: 372 AN: 2110

Alfa AF: 0.182 Hom.: 399

Bravo AF: 0.155

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		-0.16
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: rs2241704; hg19: chr19-39396335;