Variant chr11-118312086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.740

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
CD3E	NM_000733.4 linkuse as main transcript	c.86-67G>A		intron_variant		ENST00000361763.9	NP_000724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9 linkuse as main transcript	c.86-67G>A		intron_variant		1	NM_000733.4	ENSP00000354566	P1

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92551

AN:

151850

Hom.:

29066

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.612

AC XY:

45427

AN XY:

74282

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over