11-118312086-G-A

Variant names:

• chr11-118312086-G-A
• rs1945764
• NM_000733.4:c.86-67G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000733.4(CD3E):​c.86-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,445,182 control chromosomes in the GnomAD database, including 314,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29118 hom., cov: 31)
  • Exomes 𝑓: 0.66 (285822 hom.)
• Consequence: CD3E NM_000733.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.740
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-118312086-G-A is Benign according to our data. Variant chr11-118312086-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3E	NM_000733.4	c.86-67G>A		intron_variant	Intron 4 of 8	ENST00000361763.9	NP_000724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9	c.86-67G>A		intron_variant	Intron 4 of 8	1	NM_000733.4	ENSP00000354566.4

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92551 AN: 151850 Hom.: 29066 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.663 AC: 856995 AN: 1293214 Hom.: 285822 AF XY: 0.667 AC XY: 434541 AN XY: 651792

African (AFR) AF: 0.444 AC: 13359 AN: 30080

American (AMR) AF: 0.704 AC: 31343 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 18568 AN: 25150

East Asian (EAS) AF: 0.742 AC: 28783 AN: 38766

South Asian (SAS) AF: 0.745 AC: 61548 AN: 82648

European-Finnish (FIN) AF: 0.663 AC: 35252 AN: 53208

Middle Eastern (MID) AF: 0.649 AC: 3034 AN: 4674

European-Non Finnish (NFE) AF: 0.655 AC: 628906 AN: 959568

Other (OTH) AF: 0.663 AC: 36202 AN: 54630

GnomAD4 genome AF: 0.610 AC: 92667 AN: 151968 Hom.: 29118 Cov.: 31 AF XY: 0.612 AC XY: 45427 AN XY: 74282

African (AFR) AF: 0.451 AC: 18674 AN: 41414

American (AMR) AF: 0.658 AC: 10043 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2528 AN: 3472

East Asian (EAS) AF: 0.745 AC: 3853 AN: 5174

South Asian (SAS) AF: 0.741 AC: 3568 AN: 4816

European-Finnish (FIN) AF: 0.678 AC: 7151 AN: 10550

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44692 AN: 67966

Other (OTH) AF: 0.637 AC: 1342 AN: 2106

Alfa AF: 0.643 Hom.: 88190

Bravo AF: 0.603

Asia WGS AF: 0.739 AC: 2573 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.48
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1945764; hg19: chr11-118182801; COSMIC: COSV62346340; COSMIC: COSV62346340;