rs2255301

chr12-6800276-T-Cchr12-6800276-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000616.5(CD4):c.50-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,611,968 control chromosomes in the GnomAD database, including 318,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28733 hom., cov: 28)
  • Exomes 𝑓: 0.63 (289803 hom.)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.374

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-6800276-T-C is Benign according to our data. Variant chr12-6800276-T-C is described in ClinVar as [Benign]. Clinvar id is 2688003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD4	NM_000616.5	c.50-31T>C		intron_variant		ENST00000011653.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD4	ENST00000011653.9	c.50-31T>C		intron_variant		1	NM_000616.5	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92922 AN: 151480 Hom.: 28726 Cov.: 28

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.595 AC: 149013 AN: 250586 Hom.: 45046 AF XY: 0.592 AC XY: 80244 AN XY: 135454

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.610

Gnomad SAS exome AF: 0.475

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.594

GnomAD4 exome AF: 0.628 AC: 916622 AN: 1460370 Hom.: 289803 Cov.: 39 AF XY: 0.623 AC XY: 452853 AN XY: 726550

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.652

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.613 AC: 92980 AN: 151598 Hom.: 28733 Cov.: 28 AF XY: 0.609 AC XY: 45070 AN XY: 74050

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.606

Alfa AF: 0.628 Hom.: 8477

Bravo AF: 0.611

Asia WGS AF: 0.526 AC: 1827 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.0
Dann	Benign	0.67

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: rs2255301; hg19: chr12-6909442;