19-38908009-T-G

Variant names:

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

Variant summary

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

The ENST00000572515.5(NFKBIB):​c.*302T>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 0.00000102 in 980,578 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000010 (0 hom.)
• Consequence: NFKBIB ENST00000572515.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 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: 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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572515.5. 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.969+350T>G		intron	N/A	NP_002494.2
	NFKBIB	NR_040515.2		n.1327T>G		non_coding_transcript_exon	Exon 5 of 5
	NFKBIB	NM_001369699.1		c.*302T>G		3_prime_UTR	Exon 5 of 5	NP_001356628.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIB	ENST00000572515.5	TSL:1	c.*302T>G		3_prime_UTR	Exon 5 of 5	ENSP00000459728.1
	NFKBIB	ENST00000313582.6	TSL:1 MANE Select	c.969+350T>G		intron	N/A	ENSP00000312988.5
	NFKBIB	ENST00000509705.3	TSL:2	n.*1065T>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000438598.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 980578 Hom.: 0 Cov.: 31 AF XY: 0.00000217 AC XY: 1 AN XY: 460522

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20932

American (AMR) AF: 0.00 AC: 0 AN: 7026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10142

East Asian (EAS) AF: 0.00 AC: 0 AN: 13544

South Asian (SAS) AF: 0.0000342 AC: 1 AN: 29280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 852250

Other (OTH) AF: 0.00 AC: 0 AN: 36412

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
DANN	Benign	0.53
PhyloP100		-1.1

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;