12-6816159-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000616.5(CD4):c.711G>A(p.Glu237=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,614,204 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 0 hom. )
Consequence
CD4
NM_000616.5 synonymous
NM_000616.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.536
Genes affected
CD4 (HGNC:1678): (CD4 molecule) This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 12-6816159-G-A is Benign according to our data. Variant chr12-6816159-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 742540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.536 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CD4 | NM_000616.5 | c.711G>A | p.Glu237= | synonymous_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.711G>A | p.Glu237= | synonymous_variant | 6/10 | 1 | NM_000616.5 | ENSP00000011653 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 217AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000493 AC: 124AN: 251466Hom.: 0 AF XY: 0.000390 AC XY: 53AN XY: 135904
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GnomAD4 exome AF: 0.000369 AC: 539AN: 1461886Hom.: 0 Cov.: 34 AF XY: 0.000333 AC XY: 242AN XY: 727246
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GnomAD4 genome AF: 0.00144 AC: 219AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | CD4: BP4, BP7 - |
CD4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 12, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at