chr17-16939591-C-G
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_012452.3(TNFRSF13B):c.838G>C(p.Gly280Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012452.3 missense
Scores
Clinical Significance
Conservation
Publications
- immunodeficiency, common variable, 2Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
- common variable immunodeficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000201 AC: 5AN: 248522 AF XY: 0.0000223 show subpopulations
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461296Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 726910 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74328 show subpopulations
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 2 Uncertain:1
This sequence change replaces glycine with arginine at codon 280 of the TNFRSF13B protein (p.Gly280Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs374957601, ExAC 0.003%). This missense change has been observed in individual(s) with a TNFRSF13B-related disease (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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