NM_000616.5:c.50-31T>C

Variant names:

• chr12-6800276-T-C
• rs2255301
• NM_000616.5:c.50-31T>C

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 rank	MANE	Protein	UniProt
CD4	NM_000616.5	c.50-31T>C		intron_variant	Intron 2 of 9	ENST00000011653.9	NP_000607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD4	ENST00000011653.9	c.50-31T>C		intron_variant	Intron 2 of 9	1	NM_000616.5	ENSP00000011653.4

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;