19-38900291-C-T

Variant names:

• chr19-38900291-C-T
• rs2053071
• NM_002503.5:c.179+80C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002503.5(NFKBIB):​c.179+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFKBIB NM_002503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 18 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]

SIRT2 (HGNC:10886): (sirtuin 2) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	NM_002503.5	MANE Select	c.179+80C>T		intron	N/A	NP_002494.2
	NFKBIB	NM_001369699.1		c.179+80C>T		intron	N/A	NP_001356628.1	Q15653-2
	NFKBIB	NM_001243116.2		c.-80+552C>T		intron	N/A	NP_001230045.1	G5E9C2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	ENST00000313582.6	TSL:1 MANE Select	c.179+80C>T		intron	N/A	ENSP00000312988.5	Q15653-1
	NFKBIB	ENST00000572515.5	TSL:1	c.179+80C>T		intron	N/A	ENSP00000459728.1	Q15653-2
	SIRT2	ENST00000872145.1		c.-674-96G>A		intron	N/A	ENSP00000542204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.95e-7 AC: 1 AN: 1258640 Hom.: 0 AF XY: 0.00000163 AC XY: 1 AN XY: 614424

African (AFR) AF: 0.00 AC: 0 AN: 26754

American (AMR) AF: 0.00 AC: 0 AN: 20562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19216

East Asian (EAS) AF: 0.00 AC: 0 AN: 32966

South Asian (SAS) AF: 0.00 AC: 0 AN: 65682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 999078

Other (OTH) AF: 0.00 AC: 0 AN: 52666

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		-0.45
PromoterAI		-0.0028	Neutral

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: rs2053071; hg19: chr19-39390931;