12-6796549-T-C

Variant names:

• chr12-6796549-T-C
• rs1075838
• NM_000616.5:c.-67-3523T>C

Variant summary

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

The NM_000616.5(CD4):​c.-67-3523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,908 control chromosomes in the GnomAD database, including 30,695 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 0.63 (30695 hom., cov: 31)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 4 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: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (AFR) allele frequency at 95% confidence interval = 0.668 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	NM_000616.5	MANE Select	c.-67-3523T>C		intron	N/A	NP_000607.1	P01730
	CD4	NM_001382707.1		c.-153-2989T>C		intron	N/A	NP_001369636.1	P01730
	CD4	NM_001382714.1		c.-67-3523T>C		intron	N/A	NP_001369643.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000011653.9	TSL:1 MANE Select	c.-67-3523T>C		intron	N/A	ENSP00000011653.4	P01730
	CD4	ENST00000541982.5	TSL:1	c.-67-3523T>C		intron	N/A	ENSP00000445167.1	F5H480
	CD4	ENST00000538827.5	TSL:1	n.127+6887T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96176 AN: 151790 Hom.: 30689 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.633 AC: 96222 AN: 151908 Hom.: 30695 Cov.: 31 AF XY: 0.629 AC XY: 46686 AN XY: 74226

African (AFR) AF: 0.675 AC: 27936 AN: 41390

American (AMR) AF: 0.580 AC: 8842 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2411 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1866 AN: 5154

South Asian (SAS) AF: 0.587 AC: 2823 AN: 4808

European-Finnish (FIN) AF: 0.659 AC: 6960 AN: 10554

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43181 AN: 67962

Other (OTH) AF: 0.629 AC: 1329 AN: 2114

Alfa AF: 0.625 Hom.: 4962

Bravo AF: 0.629

Asia WGS AF: 0.491 AC: 1712 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	4.9
DANN	Benign	0.63
PhyloP100		0.14
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: rs1075838; hg19: chr12-6905715;