rs199912925
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_005214.5(CTLA4):c.565A>G(p.Met189Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000217 in 1,610,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005214.5 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTLA4 | NM_005214.5 | c.565A>G | p.Met189Val | missense_variant, splice_region_variant | 3/4 | ENST00000648405.2 | NP_005205.2 | |
CTLA4 | NM_001037631.3 | c.457+552A>G | intron_variant | NP_001032720.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTLA4 | ENST00000648405.2 | c.565A>G | p.Met189Val | missense_variant, splice_region_variant | 3/4 | NM_005214.5 | ENSP00000497102.1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251222Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135748
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1458374Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 725764
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74264
ClinVar
Submissions by phenotype
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 10, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 542068). This variant has not been reported in the literature in individuals affected with CTLA4-related conditions. This variant is present in population databases (rs199912925, gnomAD 0.02%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 189 of the CTLA4 protein (p.Met189Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at