rs3216776

Variant names:

• chr12-6800214-TG-T
• rs3216776
• NM_000616.5:c.49+28delG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000616.5(CD4):​c.49+28delG 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
• Publications: 4 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: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	NM_000616.5	MANE Select	c.49+28delG		intron	N/A	NP_000607.1	P01730
	CD4	NM_001382707.1		c.49+28delG		intron	N/A	NP_001369636.1	P01730
	CD4	NM_001382714.1		c.49+28delG		intron	N/A	NP_001369643.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000011653.9	TSL:1 MANE Select	c.49+28delG		intron	N/A	ENSP00000011653.4	P01730
	CD4	ENST00000541982.5	TSL:1	c.49+28delG		intron	N/A	ENSP00000445167.1	F5H480
	CD4	ENST00000538827.5	TSL:1	n.127+10553delG		intron	N/A

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

GnomAD2 exomes AF: 0.581 AC: 146021 AN: 251130 AF XY: 0.583

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 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

African (AFR) AF: 0.421 AC: 14083 AN: 33452

American (AMR) AF: 0.504 AC: 22527 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14785 AN: 26132

East Asian (EAS) AF: 0.652 AC: 25884 AN: 39696

South Asian (SAS) AF: 0.476 AC: 41018 AN: 86218

European-Finnish (FIN) AF: 0.623 AC: 33190 AN: 53310

Middle Eastern (MID) AF: 0.576 AC: 3323 AN: 5768

European-Non Finnish (NFE) AF: 0.647 AC: 718140 AN: 1110672

Other (OTH) AF: 0.593 AC: 35787 AN: 60338

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

African (AFR) AF: 0.425 AC: 17526 AN: 41254

American (AMR) AF: 0.551 AC: 8371 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1920 AN: 3462

East Asian (EAS) AF: 0.620 AC: 3172 AN: 5114

South Asian (SAS) AF: 0.466 AC: 2231 AN: 4788

European-Finnish (FIN) AF: 0.612 AC: 6441 AN: 10520

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43866 AN: 67822

Other (OTH) AF: 0.577 AC: 1215 AN: 2106

Alfa AF: 0.321 Hom.: 2695

Bravo AF: 0.556

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 79 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
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: rs3216776; hg19: chr12-6909380; COSMIC: COSV107207713;