NM_000733.4:c.568-282A>G

Variant names:

• chr11-118315204-A-G
• rs3782042
• NM_000733.4:c.568-282A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000733.4(CD3E):​c.568-282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,890 control chromosomes in the GnomAD database, including 22,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22760 hom., cov: 30)
• Consequence: CD3E NM_000733.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.574
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-118315204-A-G is Benign according to our data. Variant chr11-118315204-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	NM_000733.4	MANE Select	c.568-282A>G		intron	N/A	NP_000724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	ENST00000361763.9	TSL:1 MANE Select	c.568-282A>G		intron	N/A	ENSP00000354566.4
	CD3E	ENST00000528600.1	TSL:5	c.550-282A>G		intron	N/A	ENSP00000433975.1
	CD3E	ENST00000526146.5	TSL:2	n.1954-282A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78453 AN: 151772 Hom.: 22753 Cov.: 30

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.517 AC: 78484 AN: 151890 Hom.: 22760 Cov.: 30 AF XY: 0.520 AC XY: 38626 AN XY: 74242

African (AFR) AF: 0.240 AC: 9937 AN: 41410

American (AMR) AF: 0.660 AC: 10071 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2389 AN: 5164

South Asian (SAS) AF: 0.562 AC: 2703 AN: 4806

European-Finnish (FIN) AF: 0.626 AC: 6595 AN: 10538

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43109 AN: 67944

Other (OTH) AF: 0.543 AC: 1142 AN: 2104

Alfa AF: 0.588 Hom.: 5608

Bravo AF: 0.506

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 02, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		-0.57
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: rs3782042; hg19: chr11-118185919;