12-6800214-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000616.5(CD4):c.49+28del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24846 hom., cov: 0)
  • Exomes 𝑓: 0.62 (285692 hom.)
• Consequence: CD4 NM_000616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.358

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 -16 ACMG points.

• BP6: Variant 12-6800214-TG-T is Benign according to our data. Variant chr12-6800214-TG-T is described in ClinVar as [Benign]. Clinvar id is 1192704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD4	NM_000616.5	c.49+28del		intron_variant		ENST00000011653.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD4	ENST00000011653.9	c.49+28del		intron_variant		1	NM_000616.5	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85404 AN: 151358 Hom.: 24844 Cov.: 0

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.581 AC: 146021 AN: 251130 Hom.: 43376 AF XY: 0.583 AC XY: 79121 AN XY: 135732

Gnomad AFR exome AF: 0.421

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.609

Gnomad SAS exome AF: 0.474

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.622 AC: 908737 AN: 1460290 Hom.: 285692 Cov.: 0 AF XY: 0.619 AC XY: 449460 AN XY: 726504

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.652

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.564 AC: 85447 AN: 151476 Hom.: 24846 Cov.: 0 AF XY: 0.563 AC XY: 41608 AN XY: 73944

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.577

Alfa AF: 0.321 Hom.: 2695

Bravo AF: 0.556

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. -

Immunodeficiency 79 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs3216776; hg19: chr12-6909380;