2-112836202-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000576.3(IL1B):c.28G>A(p.Glu10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_000576.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251464Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135904
GnomAD4 exome AF: 0.0000766 AC: 112AN: 1461432Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 81AN XY: 727018
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1
The IL1B p.Glu10Lys variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs376289593), LOVD 3.0 and in control databases in 29 of 251464 chromosomes at a frequency of 0.000115 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 24 of 30616 chromosomes (freq: 0.000784), Other in 2 of 6138 chromosomes (freq: 0.000326) and European (non-Finnish) in 3 of 113746 chromosomes (freq: 0.000026), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, and European (Finnish) populations. The p.Glu10 residue is not conserved in mammals and four out of five computational analyses (SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at