rs1055141

Variant names:

• chr12-6817197-T-C
• rs1055141
• NM_000616.5:c.1023T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000616.5(CD4):​c.1023T>C​(p.Ser341Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,520 control chromosomes in the GnomAD database, including 283,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32183 hom., cov: 32)
  • Exomes 𝑓: 0.58 (251612 hom.)
• Consequence: CD4 NM_000616.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.232
• Publications: 29 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-6817197-T-C is Benign according to our data. Variant chr12-6817197-T-C is described in ClinVar as Benign. ClinVar VariationId is 1192706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.232 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 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.1023T>C	p.Ser341Ser	synonymous	Exon 7 of 10	NP_000607.1	P01730
	CD4	NM_001382707.1		c.1023T>C	p.Ser341Ser	synonymous	Exon 8 of 11	NP_001369636.1	P01730
	CD4	NM_001382714.1		c.858T>C	p.Ser286Ser	synonymous	Exon 6 of 9	NP_001369643.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD4	ENST00000011653.9	TSL:1 MANE Select	c.1023T>C	p.Ser341Ser	synonymous	Exon 7 of 10	ENSP00000011653.4	P01730
	CD4	ENST00000872060.1		c.1023T>C	p.Ser341Ser	synonymous	Exon 8 of 11	ENSP00000542119.1
	CD4	ENST00000872059.1		c.858T>C	p.Ser286Ser	synonymous	Exon 6 of 9	ENSP00000542118.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97451 AN: 151924 Hom.: 32156 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.644 AC: 161626 AN: 250894 AF XY: 0.640

Gnomad AFR exome AF: 0.755

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.583

Gnomad EAS exome AF: 0.928

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.581 AC: 848783 AN: 1461478 Hom.: 251612 Cov.: 52 AF XY: 0.584 AC XY: 424404 AN XY: 727034

African (AFR) AF: 0.757 AC: 25328 AN: 33480

American (AMR) AF: 0.680 AC: 30358 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 15038 AN: 26134

East Asian (EAS) AF: 0.906 AC: 35967 AN: 39700

South Asian (SAS) AF: 0.705 AC: 60830 AN: 86244

European-Finnish (FIN) AF: 0.660 AC: 35265 AN: 53398

Middle Eastern (MID) AF: 0.616 AC: 3554 AN: 5768

European-Non Finnish (NFE) AF: 0.545 AC: 606109 AN: 1111722

Other (OTH) AF: 0.602 AC: 36334 AN: 60374

GnomAD4 genome AF: 0.642 AC: 97542 AN: 152042 Hom.: 32183 Cov.: 32 AF XY: 0.650 AC XY: 48326 AN XY: 74330

African (AFR) AF: 0.752 AC: 31172 AN: 41456

American (AMR) AF: 0.629 AC: 9616 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3468

East Asian (EAS) AF: 0.919 AC: 4760 AN: 5178

South Asian (SAS) AF: 0.717 AC: 3459 AN: 4824

European-Finnish (FIN) AF: 0.666 AC: 7040 AN: 10570

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37522 AN: 67948

Other (OTH) AF: 0.621 AC: 1310 AN: 2110

Alfa AF: 0.584 Hom.: 25223

Bravo AF: 0.644

Asia WGS AF: 0.782 AC: 2722 AN: 3478

EpiCase AF: 0.548

EpiControl AF: 0.554

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.1
DANN	Benign	0.67
PhyloP100		0.23
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: rs1055141; hg19: chr12-6926363; COSMIC: COSV108007227; COSMIC: COSV108007227;