11-118313861-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000733.4(CD3E):c.507C>T(p.Gly169Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,244 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G169G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 113 hom. )

Consequence

CD3E
NM_000733.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.69

Publications

5 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: Labcorp Genetics (formerly Invitae), ClinGen
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=-0.66).

BP6

Variant 11-118313861-C-T is Benign according to our data. Variant chr11-118313861-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 35807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00853 (1299/152232) while in subpopulation SAS AF = 0.0149 (72/4828). AF 95% confidence interval is 0.0121. There are 10 homozygotes in GnomAd4. There are 701 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000733.4. 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
	CD3E	NM_000733.4	MANE Select	c.507C>T	p.Gly169Gly	synonymous	Exon 7 of 9	NP_000724.1	P07766

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD3E	ENST00000361763.9	TSL:1 MANE Select	c.507C>T	p.Gly169Gly	synonymous	Exon 7 of 9	ENSP00000354566.4	P07766
CD3E	ENST00000853938.1		c.507C>T	p.Gly169Gly	synonymous	Exon 6 of 8	ENSP00000523997.1
CD3E	ENST00000528600.1	TSL:5	c.489C>T	p.Gly163Gly	synonymous	Exon 5 of 7	ENSP00000433975.1	E9PSH8

Frequencies

GnomAD3 genomes

AF:

0.00851

AC:

1295

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00943

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00909

GnomAD2 exomes

AF:

0.0105

AC:

2630

AN:

251152

AF XY:

0.0115

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.00500

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.00994

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0113

AC:

16524

AN:

1461012

Hom.:

113

Cov.:

AF XY:

0.0115

AC XY:

8374

AN XY:

726826

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33452

American (AMR)

AF:

0.00364

AC:

163

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

730

AN:

26136

East Asian (EAS)

AF:

0.0139

AC:

550

AN:

39700

South Asian (SAS)

AF:

0.0173

AC:

1494

AN:

86216

European-Finnish (FIN)

AF:

0.0152

AC:

811

AN:

53374

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5124

European-Non Finnish (NFE)

AF:

0.0107

AC:

11905

AN:

1111978

Other (OTH)

AF:

0.0125

AC:

756

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

985

1970

2954

3939

4924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.00853

AC:

1299

AN:

152232

Hom.:

Cov.:

AF XY:

0.00942

AC XY:

701

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

41536

American (AMR)

AF:

0.00425

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3472

East Asian (EAS)

AF:

0.00946

AC:

AN:

5182

South Asian (SAS)

AF:

0.0149

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0216

AC:

229

AN:

10594

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0103

AC:

702

AN:

68016

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0100

Hom.:

Bravo

AF:

0.00675

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.00943

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 18 (2)

not provided (2)

Severe combined immunodeficiency disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.73

(source)

DANN

Benign

0.51

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over