12-6800139-A-G
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000616.5(CD4):āc.1A>Gā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000161 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000016 ( 0 hom. )
Consequence
CD4
NM_000616.5 start_lost
NM_000616.5 start_lost
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 3.85
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 Pathogenic. Variant got 11 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-6800139-A-G is Pathogenic according to our data. Variant chr12-6800139-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1048527.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CD4 | NM_000616.5 | c.1A>G | p.Met1? | start_lost | 2/10 | ENST00000011653.9 | NP_000607.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CD4 | ENST00000011653.9 | c.1A>G | p.Met1? | start_lost | 2/10 | 1 | NM_000616.5 | ENSP00000011653 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251348Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135842
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461764Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 727176
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 79 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 26, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of catalytic residue at V5 (P = 0.0083);Gain of catalytic residue at V5 (P = 0.0083);Gain of catalytic residue at V5 (P = 0.0083);
MVP
ClinPred
D
GERP RS
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Splicing
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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