12-6816241-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000616.5(CD4):c.793C>T(p.Arg265Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,120 control chromosomes in the GnomAD database, including 1,611 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000616.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CD4 | NM_000616.5 | c.793C>T | p.Arg265Trp | missense_variant | 6/10 | ENST00000011653.9 | NP_000607.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CD4 | ENST00000011653.9 | c.793C>T | p.Arg265Trp | missense_variant | 6/10 | 1 | NM_000616.5 | ENSP00000011653 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0596 AC: 9064AN: 152120Hom.: 831 Cov.: 32
GnomAD3 exomes AF: 0.0191 AC: 4780AN: 250838Hom.: 358 AF XY: 0.0151 AC XY: 2050AN XY: 135646
GnomAD4 exome AF: 0.00851 AC: 12438AN: 1461882Hom.: 777 Cov.: 34 AF XY: 0.00779 AC XY: 5664AN XY: 727242
GnomAD4 genome AF: 0.0597 AC: 9083AN: 152238Hom.: 834 Cov.: 32 AF XY: 0.0580 AC XY: 4318AN XY: 74442
ClinVar
Submissions by phenotype
Okt4 epitope deficiency Pathogenic:1Benign:1
Benign, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_000616.4:c.793C>T (p.Arg265Trp) in the gene CD4 was reported as c.867G>A (p.Arg240Trp). Hodge et al reported this variant in a OKT4-Epitope deficiency patient (PMID: 1708753). In addition, Takenaka et al. reported homozygosity of this variant in patients with OKT4 epitope deficiency (PMID: 7689618). It has an allele frequency of 0.201 in African subpopulation in the gnomAD database. 516 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1; BS2; PM3_Supporting; PP4. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1993 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | research | H3Africa Consortium | Oct 28, 2020 | While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.188, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. - |
CD4-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at