rs1945764

Positions:

• chr11-118312086-G-A
• chr11-118312086-G-C

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.740

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
CD3E	NM_000733.4	c.86-67G>A		intron_variant		ENST00000361763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD3E	ENST00000361763.9	c.86-67G>A		intron_variant		1	NM_000733.4	P1

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

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.663

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

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.637

Alfa AF: 0.658 Hom.: 55123

Bravo AF: 0.603

Asia WGS AF: 0.739 AC: 2573 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.48

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

LitVar

Other links and lift over

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