19-38908764-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002503.5(NFKBIB):c.1003C>T(p.Arg335Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002503.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKBIB | NM_002503.5 | c.1003C>T | p.Arg335Cys | missense_variant | 6/6 | ENST00000313582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKBIB | ENST00000313582.6 | c.1003C>T | p.Arg335Cys | missense_variant | 6/6 | 1 | NM_002503.5 | P1 | |
NFKBIB | ENST00000392079.7 | c.745C>T | p.Arg249Cys | missense_variant | 6/6 | 5 | |||
NFKBIB | ENST00000509705.3 | c.*1820C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152034Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251152Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135740
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461618Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727088
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152034Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74246
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2022 | The c.1003C>T (p.R335C) alteration is located in exon 6 (coding exon 6) of the NFKBIB gene. This alteration results from a C to T substitution at nucleotide position 1003, causing the arginine (R) at amino acid position 335 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at