12-6810153-G-C

Variant names:

• chr12-6810153-G-C
• rs11575097
• NM_000616.5:c.215-3989G>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.215-3989G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 149,892 control chromosomes in the GnomAD database, including 1,300 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 0.10 (1300 hom., cov: 30)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.215-3989G>C		intron	N/A	NP_000607.1
	CD4	NM_001382707.1		c.215-3989G>C		intron	N/A	NP_001369636.1
	CD4	NM_001382714.1		c.50-3989G>C		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.215-3989G>C		intron	N/A	ENSP00000011653.4
	CD4	ENST00000541982.5	TSL:1	c.50-3989G>C		intron	N/A	ENSP00000445167.1
	CD4	ENST00000538827.5	TSL:1	n.128-3989G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.100 AC: 14974 AN: 149774 Hom.: 1295 Cov.: 30

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0895

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

GnomAD4 genome AF: 0.100 AC: 15002 AN: 149892 Hom.: 1300 Cov.: 30 AF XY: 0.103 AC XY: 7503 AN XY: 73120

African (AFR) AF: 0.230 AC: 9372 AN: 40770

American (AMR) AF: 0.0593 AC: 880 AN: 14836

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 152 AN: 3450

East Asian (EAS) AF: 0.170 AC: 857 AN: 5052

South Asian (SAS) AF: 0.168 AC: 786 AN: 4688

European-Finnish (FIN) AF: 0.0480 AC: 495 AN: 10312

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2173 AN: 67526

Other (OTH) AF: 0.0914 AC: 188 AN: 2056

Alfa AF: 0.0216 Hom.: 24

Bravo AF: 0.102

Asia WGS AF: 0.175 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.75
PhyloP100		-1.7
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: rs11575097; hg19: chr12-6919319;