12-6792836-G-T

Position:

• chr12-6792836-G-T

Variant summary

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

The NM_000616.5(CD4):​c.-68+3174G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,922 control chromosomes in the GnomAD database, including 20,600 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 0.52 (20600 hom., cov: 31)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD4	NM_000616.5	c.-68+3174G>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.-68+3174G>T		intron_variant		1	NM_000616.5	ENSP00000011653.4

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78349 AN: 151804 Hom.: 20573 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.516 AC: 78414 AN: 151922 Hom.: 20600 Cov.: 31 AF XY: 0.521 AC XY: 38662 AN XY: 74238

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.509

Alfa AF: 0.464 Hom.: 21206

Bravo AF: 0.516

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.41

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: rs2707210; hg19: chr12-6902002;