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12-6814296-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000616.5(CD4):c.369C>T(p.Phe123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,462 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 19 hom., cov: 31)
Exomes 𝑓: 0.00099 ( 15 hom. )

Consequence

CD4
NM_000616.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0860
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 -15 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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6814296-C-T is Benign according to our data. Variant chr12-6814296-C-T is described in ClinVar as [Benign]. Clinvar id is 714504.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=0.086 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00956 (1454/152160) while in subpopulation AFR AF= 0.0326 (1353/41472). AF 95% confidence interval is 0.0312. There are 19 homozygotes in gnomad4. There are 663 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD4NM_000616.5 linkuse as main transcriptc.369C>T p.Phe123= synonymous_variant 4/10 ENST00000011653.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD4ENST00000011653.9 linkuse as main transcriptc.369C>T p.Phe123= synonymous_variant 4/101 NM_000616.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00958
AC:
1456
AN:
152042
Hom.:
19
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0328
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00511
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00239
AC:
599
AN:
250786
Hom.:
4
AF XY:
0.00152
AC XY:
206
AN XY:
135572
show subpopulations
Gnomad AFR exome
AF:
0.0326
Gnomad AMR exome
AF:
0.00148
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000994
AC:
1453
AN:
1461302
Hom.:
15
Cov.:
32
AF XY:
0.000846
AC XY:
615
AN XY:
726916
show subpopulations
Gnomad4 AFR exome
AF:
0.0333
Gnomad4 AMR exome
AF:
0.00226
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000918
Gnomad4 OTH exome
AF:
0.00207
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00956
AC:
1454
AN:
152160
Hom.:
19
Cov.:
31
AF XY:
0.00891
AC XY:
663
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0326
Gnomad4 AMR
AF:
0.00510
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00282
Hom.:
2
Bravo
AF:
0.0110
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
13
Dann
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs11064416; hg19: chr12-6923462; API