12-6789226-A-G

Variant names:

• chr12-6789226-A-G
• rs11064392
• ENST00000535707.5:n.149-263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000535707.5(CD4):​n.149-263A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 10 publications found

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]

CD4 Gene-Disease associations (from GenCC):

• immunodeficiency 79

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535707.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000535707.5	TSL:4	n.149-263A>G		intron	N/A

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

African (AFR) AF: 0.143 AC: 5923 AN: 41526

American (AMR) AF: 0.101 AC: 1548 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1891 AN: 5172

South Asian (SAS) AF: 0.184 AC: 886 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1836 AN: 10594

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9552 AN: 68002

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.145 Hom.: 245

Bravo AF: 0.139

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.32
PhyloP100		-0.71
PromoterAI		-0.0050	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11064392; hg19: chr12-6898392;