rs2255301

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-6800276-T-C
• chr12-6800276-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 79

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes AF: 0.595 AC: 149013 AN: 250586 AF XY: 0.592

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 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

African (AFR) AF: 0.595 AC: 19889 AN: 33442

American (AMR) AF: 0.514 AC: 22968 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14865 AN: 26114

East Asian (EAS) AF: 0.652 AC: 25879 AN: 39678

South Asian (SAS) AF: 0.477 AC: 41095 AN: 86218

European-Finnish (FIN) AF: 0.622 AC: 33056 AN: 53120

Middle Eastern (MID) AF: 0.587 AC: 3386 AN: 5768

European-Non Finnish (NFE) AF: 0.647 AC: 719000 AN: 1110976

Other (OTH) AF: 0.604 AC: 36484 AN: 60358

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

African (AFR) AF: 0.595 AC: 24580 AN: 41342

American (AMR) AF: 0.569 AC: 8653 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3464

East Asian (EAS) AF: 0.622 AC: 3194 AN: 5136

South Asian (SAS) AF: 0.466 AC: 2228 AN: 4780

European-Finnish (FIN) AF: 0.613 AC: 6421 AN: 10482

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 43979 AN: 67862

Other (OTH) AF: 0.606 AC: 1278 AN: 2110

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
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2255301; hg19: chr12-6909442; COSMIC: COSV107207714;