12-6816147-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000616.5(CD4):​c.699G>T​(p.Thr233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,150 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 96 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 89 hom. )

Consequence

CD4
NM_000616.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.139
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 12-6816147-G-T is Benign according to our data. Variant chr12-6816147-G-T is described in ClinVar as [Benign]. Clinvar id is 789805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.139 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CD4NM_000616.5 linkuse as main transcriptc.699G>T p.Thr233= synonymous_variant 6/10 ENST00000011653.9 NP_000607.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CD4ENST00000011653.9 linkuse as main transcriptc.699G>T p.Thr233= synonymous_variant 6/101 NM_000616.5 ENSP00000011653 P1

Frequencies

GnomAD3 genomes
AF:
0.0206
AC:
3127
AN:
152152
Hom.:
96
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0703
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0103
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.0148
GnomAD3 exomes
AF:
0.00526
AC:
1322
AN:
251470
Hom.:
40
AF XY:
0.00363
AC XY:
493
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0714
Gnomad AMR exome
AF:
0.00289
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000457
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00230
AC:
3358
AN:
1461880
Hom.:
89
Cov.:
34
AF XY:
0.00198
AC XY:
1437
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0724
Gnomad4 AMR exome
AF:
0.00418
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000410
Gnomad4 OTH exome
AF:
0.00439
GnomAD4 genome
AF:
0.0206
AC:
3136
AN:
152270
Hom.:
96
Cov.:
32
AF XY:
0.0200
AC XY:
1491
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0703
Gnomad4 AMR
AF:
0.0103
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.0147
Alfa
AF:
0.00376
Hom.:
2
Bravo
AF:
0.0242
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000818
EpiControl
AF:
0.000652

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 06, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.1
DANN
Benign
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs10849525; hg19: chr12-6925313; API