rs11064392

chr12-6789226-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000535707.5(CD4):n.149-263A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,200 control chromosomes in the GnomAD database, including 1,833 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1833 hom., cov: 32)
• Consequence: CD4 ENST00000535707.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD4	ENST00000535707.5	n.149-263A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22286 AN: 152082 Hom.: 1831 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22296 AN: 152200 Hom.: 1833 Cov.: 32 AF XY: 0.148 AC XY: 11008 AN XY: 74408

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0830

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.131

Alfa AF: 0.141 Hom.: 125

Bravo AF: 0.139

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.40
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11064392; hg19: chr12-6898392;