Variant 12-6815983-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000541982.5(CD4):c.*248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,592,804 control chromosomes in the GnomAD database, including 97,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 7207 hom., cov: 31)

Exomes 𝑓: 0.35 ( 89811 hom. )

Consequence

CD4
ENST00000541982.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.290

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-6815983-C-T is Benign according to our data. Variant chr12-6815983-C-T is described in ClinVar as [Benign]. Clinvar id is 2688100.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD4	NM_000616.5 linkuse as main transcript	c.608-73C>T		intron_variant		ENST00000011653.9	NP_000607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD4	ENST00000011653.9 linkuse as main transcript	c.608-73C>T		intron_variant		1	NM_000616.5	ENSP00000011653	P1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43922

AN:

151896

Hom.:

7202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.336

AC:

74883

AN:

222906

Hom.:

13278

AF XY:

0.330

AC XY:

39860

AN XY:

120606

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.348

AC:

501355

AN:

1440790

Hom.:

89811

Cov.:

AF XY:

0.344

AC XY:

246391

AN XY:

715268

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.289

AC:

43951

AN:

152014

Hom.:

7207

Cov.:

AF XY:

0.287

AC XY:

21302

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.340

Hom.:

2807

Bravo

AF:

0.285

Asia WGS

AF:

0.230

AC:

801

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

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 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 51. Only high quality variants are reported. -

CD4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over