Genetic Variant NM_000616.5:c.50-31T>C (chr12-6800276-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374

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=-0.88).

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 link	c.50-31T>C		intron_variant	Intron 2 of 9	ENST00000011653.9	NP_000607.1	P01730B4DT49A0A4Y5UGE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD4	ENST00000011653.9 link	c.50-31T>C		intron_variant	Intron 2 of 9	1	NM_000616.5	ENSP00000011653.4		P01730

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

92922

AN:

151480

Hom.:

28726

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.623

AC XY:

452853

AN XY:

726550

show subpopulations

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.:

AF XY:

0.609

AC XY:

45070

AN XY:

74050

show subpopulations

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

LINK: link

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

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