chr12-6789355-G-C

Variant names:

• chr12-6789355-G-C
• rs2855534
• ENST00000535707.5:n.149-134G>C

Variant summary

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

The ENST00000535707.5(CD4):​n.149-134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,136 control chromosomes in the GnomAD database, including 29,824 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 0.62 (29811 hom., cov: 33)
  • Exomes 𝑓: 0.72 (13 hom.)
• Consequence: CD4 ENST00000535707.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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
	CD4	NM_000616.5	MANE Select	c.-375G>C		upstream_gene	N/A	NP_000607.1
	CD4	NM_001382707.1		c.-461G>C		upstream_gene	N/A	NP_001369636.1
	CD4	NM_001382714.1		c.-375G>C		upstream_gene	N/A	NP_001369643.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000535707.5	TSL:4	n.149-134G>C		intron	N/A
	CD4	ENST00000011653.9	TSL:1 MANE Select	c.-375G>C		upstream_gene	N/A	ENSP00000011653.4
	CD4	ENST00000541982.5	TSL:1	c.-375G>C		upstream_gene	N/A	ENSP00000445167.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94696 AN: 151968 Hom.: 29784 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.720 AC: 36 AN: 50 Hom.: 13 AF XY: 0.722 AC XY: 26 AN XY: 36

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 9 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.714 AC: 20 AN: 28

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.623 AC: 94775 AN: 152086 Hom.: 29811 Cov.: 33 AF XY: 0.618 AC XY: 45953 AN XY: 74344

African (AFR) AF: 0.657 AC: 27236 AN: 41478

American (AMR) AF: 0.585 AC: 8936 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2372 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1798 AN: 5176

South Asian (SAS) AF: 0.482 AC: 2320 AN: 4810

European-Finnish (FIN) AF: 0.660 AC: 6978 AN: 10576

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42916 AN: 67984

Other (OTH) AF: 0.633 AC: 1339 AN: 2116

Alfa AF: 0.524 Hom.: 1527

Bravo AF: 0.623

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.57
PhyloP100		-1.1
PromoterAI		-0.010	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2855534; hg19: chr12-6898521;