rs1126924

Positions:

chr11-118307292-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000733.4(CD3E):c.54C>T(p.Gly18=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 302659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118307292-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CD3E	NM_000733.4 linkuse as main transcript	c.54C>T	p.Gly18=	synonymous_variant	3/9	ENST00000361763.9	NP_000724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9 linkuse as main transcript	c.54C>T	p.Gly18=	synonymous_variant	3/9	1	NM_000733.4	ENSP00000354566	P1

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

GnomAD3 exomes

AF:

0.319

AC:

79570

AN:

249668

Hom.:

14145

AF XY:

0.318

AC XY:

42886

AN XY:

135012

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 SAS exome

AF:

0.306

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

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.258

AC:

39114

AN:

151806

Hom.:

6167

Cov.:

AF XY:

0.260

AC XY:

19273

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0812

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.305

Hom.:

7056

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.2

DANN

Benign

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over