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 (★★). Synonymous variant affecting the same amino acid position (i.e. G18G) has been classified as Uncertain significance.

• 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: Labcorp Genetics (formerly Invitae), ClinGen
• 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.

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.54C>T	p.Gly18Gly	synonymous	Exon 3 of 9	NP_000724.1	P07766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	ENST00000361763.9	TSL:1 MANE Select	c.54C>T	p.Gly18Gly	synonymous	Exon 3 of 9	ENSP00000354566.4	P07766
	CD3E	ENST00000853938.1		c.54C>T	p.Gly18Gly	synonymous	Exon 2 of 8	ENSP00000523997.1
	CD3E	ENST00000528600.1	TSL:5	c.54C>T	p.Gly18Gly	synonymous	Exon 2 of 7	ENSP00000433975.1	E9PSH8

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Immunodeficiency 18 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;