rs1126924

Variant names:

• chr11-118307292-C-T
• rs1126924
• NM_000733.4:c.54C>T

Variant summary

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

The NM_000733.4(CD3E):​c.54C>T​(p.Gly18Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,593,588 control chromosomes in the GnomAD database, including 78,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6167 hom., cov: 31)
  • Exomes 𝑓: 0.31 (72437 hom.)
• Consequence: CD3E NM_000733.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.413
• Publications: 15 publications found

Genes affected

CD3E (HGNC:1674): (CD3 epsilon subunit of T-cell receptor complex) The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. The epsilon polypeptide plays an essential role in T-cell development. Defects in this gene cause immunodeficiency. This gene has also been linked to a susceptibility to type I diabetes in women. [provided by RefSeq, Jul 2008]

CD3E Gene-Disease associations (from GenCC):

• immunodeficiency 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-118307292-C-T is Benign according to our data. Variant chr11-118307292-C-T is described in ClinVar as Benign. ClinVar VariationId is 302659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.413 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3E	NM_000733.4	c.54C>T	p.Gly18Gly	synonymous_variant	Exon 3 of 9	ENST00000361763.9	NP_000724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9	c.54C>T	p.Gly18Gly	synonymous_variant	Exon 3 of 9	1	NM_000733.4	ENSP00000354566.4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39062 AN: 151688 Hom.: 6145 Cov.: 31

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.319 AC: 79570 AN: 249668 AF XY: 0.318

Gnomad AFR exome AF: 0.0723

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.310 AC: 446641 AN: 1441782 Hom.: 72437 Cov.: 30 AF XY: 0.310 AC XY: 222725 AN XY: 718224

African (AFR) AF: 0.0716 AC: 2386 AN: 33314

American (AMR) AF: 0.502 AC: 22331 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7735 AN: 25992

East Asian (EAS) AF: 0.204 AC: 8060 AN: 39584

South Asian (SAS) AF: 0.307 AC: 26236 AN: 85518

European-Finnish (FIN) AF: 0.330 AC: 17375 AN: 52646

Middle Eastern (MID) AF: 0.307 AC: 1762 AN: 5734

European-Non Finnish (NFE) AF: 0.313 AC: 343025 AN: 1094800

Other (OTH) AF: 0.297 AC: 17731 AN: 59720

GnomAD4 genome AF: 0.258 AC: 39114 AN: 151806 Hom.: 6167 Cov.: 31 AF XY: 0.260 AC XY: 19273 AN XY: 74224

African (AFR) AF: 0.0812 AC: 3359 AN: 41390

American (AMR) AF: 0.397 AC: 6043 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5162

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3515 AN: 10520

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21658 AN: 67908

Other (OTH) AF: 0.292 AC: 616 AN: 2106

Alfa AF: 0.300 Hom.: 9082

Bravo AF: 0.256

Asia WGS AF: 0.235 AC: 819 AN: 3478

EpiCase AF: 0.318

EpiControl AF: 0.320

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 12, 2023

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 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

Immunodeficiency 18 Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1126924; hg19: chr11-118178007; COSMIC: COSV62345472; COSMIC: COSV62345472;