12-6791968-C-T

Variant names:

• chr12-6791968-C-T
• rs2707212
• NM_000616.5:c.-68+2306C>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.-68+2306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,946 control chromosomes in the GnomAD database, including 6,759 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 0.28 (6759 hom., cov: 31)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 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.-68+2306C>T		intron	N/A	NP_000607.1
	CD4	NM_001382707.1		c.-154+2306C>T		intron	N/A	NP_001369636.1
	CD4	NM_001382714.1		c.-68+2306C>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.-68+2306C>T		intron	N/A	ENSP00000011653.4
	CD4	ENST00000541982.5	TSL:1	c.-68+2306C>T		intron	N/A	ENSP00000445167.1
	CD4	ENST00000538827.5	TSL:1	n.127+2306C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43285 AN: 151828 Hom.: 6763 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.285 AC: 43286 AN: 151946 Hom.: 6759 Cov.: 31 AF XY: 0.291 AC XY: 21579 AN XY: 74270

African (AFR) AF: 0.147 AC: 6091 AN: 41438

American (AMR) AF: 0.334 AC: 5096 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1819 AN: 5168

South Asian (SAS) AF: 0.405 AC: 1950 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4013 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21885 AN: 67934

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.308 Hom.: 13572

Bravo AF: 0.277

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		0.12
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: rs2707212; hg19: chr12-6901134;