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12-6816156-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_000616.5(CD4):c.708C>T(p.Gly236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,614,172 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

CD4
NM_000616.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42
Variant links:
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 -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6816156-C-T is Benign according to our data. Variant chr12-6816156-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642636.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.42 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD4NM_000616.5 linkuse as main transcriptc.708C>T p.Gly236= synonymous_variant 6/10 ENST00000011653.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD4ENST00000011653.9 linkuse as main transcriptc.708C>T p.Gly236= synonymous_variant 6/101 NM_000616.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000986
AC:
150
AN:
152172
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00304
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000306
AC:
77
AN:
251458
Hom.:
0
AF XY:
0.000221
AC XY:
30
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00203
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.000695
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000244
AC:
357
AN:
1461882
Hom.:
3
Cov.:
34
AF XY:
0.000252
AC XY:
183
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00427
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.000497
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000185
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000881
Gnomad4 OTH exome
AF:
0.000844
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000965
AC:
147
AN:
152290
Hom.:
1
Cov.:
32
AF XY:
0.000967
AC XY:
72
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00296
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000482
Hom.:
0
Bravo
AF:
0.000873
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023CD4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
4.0
Dann
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28919568; hg19: chr12-6925322; API