12-6819581-T-C

Position:

• chr12-6819581-T-C

Variant summary

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

The NM_000616.5(CD4):​c.*252T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 547,690 control chromosomes in the GnomAD database, including 43,497 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 0.36 (10824 hom., cov: 33)
  • Exomes 𝑓: 0.39 (32673 hom.)
• Consequence: CD4 NM_000616.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD4	NM_000616.5	c.*252T>C		3_prime_UTR_variant	10/10	ENST00000011653.9	NP_000607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD4	ENST00000011653.9	c.*252T>C		3_prime_UTR_variant	10/10	1	NM_000616.5	ENSP00000011653	P1
CD4	ENST00000437800.6	n.1867T>C		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54964 AN: 151964 Hom.: 10828 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.392 AC: 154984 AN: 395608 Hom.: 32673 Cov.: 2 AF XY: 0.387 AC XY: 80922 AN XY: 209018

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.0998

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.362 AC: 54983 AN: 152082 Hom.: 10824 Cov.: 33 AF XY: 0.353 AC XY: 26228 AN XY: 74336

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.0829

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.382

Alfa AF: 0.423 Hom.: 10154

Bravo AF: 0.359

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.7
DANN	Benign	0.85

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: rs3213427; hg19: chr12-6928747;