chr20-46118365-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001250.6(CD40):c.22T>G(p.Cys8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,614,100 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C8C) has been classified as Likely benign.
Frequency
Consequence
NM_001250.6 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 |
---|---|---|---|---|---|---|---|
CD40 | NM_001250.6 | c.22T>G | p.Cys8Gly | missense_variant | 1/9 | ENST00000372285.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD40 | ENST00000372285.8 | c.22T>G | p.Cys8Gly | missense_variant | 1/9 | 1 | NM_001250.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251382Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135880
GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461760Hom.: 2 Cov.: 36 AF XY: 0.0000701 AC XY: 51AN XY: 727184
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 8 of the CD40 protein (p.Cys8Gly). This variant is present in population databases (rs113207193, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CD40-related conditions. ClinVar contains an entry for this variant (Variation ID: 1401221). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at