rs12812942

Positions:

• chr12-6813328-A-T

Variant summary

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

The NM_000616.5(CD4):​c.215-814A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 150,568 control chromosomes in the GnomAD database, including 7,195 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 0.29 (7195 hom., cov: 28)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD4	NM_000616.5	c.215-814A>T		intron_variant		ENST00000011653.9	NP_000607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD4	ENST00000011653.9	c.215-814A>T		intron_variant		1	NM_000616.5	ENSP00000011653	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 43811 AN: 150450 Hom.: 7190 Cov.: 28

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.291 AC: 43837 AN: 150568 Hom.: 7195 Cov.: 28 AF XY: 0.289 AC XY: 21247 AN XY: 73470

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.291

Alfa AF: 0.329 Hom.: 1131

Bravo AF: 0.285

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs12812942; hg19: chr12-6922494;