chr11-118307292-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.413

Publications

15 publications found

Variant links:

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

CD3E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.54C>T	p.Gly18Gly	synonymous_variant	Exon 3 of 9	ENST00000361763.9	NP_000724.1	P07766

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9 link	c.54C>T	p.Gly18Gly	synonymous_variant	Exon 3 of 9	1	NM_000733.4	ENSP00000354566.4		P07766

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39062

AN:

151688

Hom.:

6145

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.310

AC XY:

222725

AN XY:

718224

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

13399

26797

40196

53594

66993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11014

22028

33042

44056

55070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.258

AC:

39114

AN:

151806

Hom.:

6167

Cov.:

AF XY:

0.260

AC XY:

19273

AN XY:

74224

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21658

AN:

67908

Other (OTH)

AF:

0.292

AC:

616

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1389

2779

4168

5558

6947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

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

(source)

DANN

Benign

0.40

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over