rs12812942

Variant names:

• chr12-6813328-A-T
• rs12812942
• NM_000616.5:c.215-814A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000616.5. 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.215-814A>T		intron	N/A	NP_000607.1
	CD4	NM_001382707.1		c.215-814A>T		intron	N/A	NP_001369636.1
	CD4	NM_001382714.1		c.50-814A>T		intron	N/A	NP_001369643.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000011653.9	TSL:1 MANE Select	c.215-814A>T		intron	N/A	ENSP00000011653.4
	CD4	ENST00000541982.5	TSL:1	c.50-814A>T		intron	N/A	ENSP00000445167.1
	CD4	ENST00000538827.5	TSL:1	n.128-814A>T		intron	N/A

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

African (AFR) AF: 0.137 AC: 5608 AN: 40874

American (AMR) AF: 0.352 AC: 5317 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1002 AN: 3460

East Asian (EAS) AF: 0.259 AC: 1325 AN: 5122

South Asian (SAS) AF: 0.208 AC: 989 AN: 4762

European-Finnish (FIN) AF: 0.384 AC: 3912 AN: 10200

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24657 AN: 67746

Other (OTH) AF: 0.291 AC: 608 AN: 2090

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.85
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12812942; hg19: chr12-6922494;