Genetic Variant CD3E:c.-60+49A>G (chr11-118304825-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000733.4(CD3E):c.-60+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 819,292 control chromosomes in the GnomAD database, including 41,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6206 hom., cov: 33)

Exomes 𝑓: 0.32 ( 35059 hom. )

Consequence

CD3E
NM_000733.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.686

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 11-118304825-A-G is Benign according to our data. Variant chr11-118304825-A-G is described in ClinVar as [Benign]. Clinvar id is 1178693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3E	NM_000733.4 link	c.-60+49A>G		intron_variant	Intron 1 of 8	ENST00000361763.9	NP_000724.1	P07766

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3E	ENST00000361763.9 link	c.-60+49A>G		intron_variant	Intron 1 of 8	1	NM_000733.4	ENSP00000354566.4		P07766

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39508

AN:

152078

Hom.:

6184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.315

AC:

210245

AN:

667096

Hom.:

35059

Cov.:

AF XY:

0.315

AC XY:

113762

AN XY:

361150

show subpopulations

Gnomad4 AFR exome

AF:

0.0886

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.260

AC:

39560

AN:

152196

Hom.:

6206

Cov.:

AF XY:

0.262

AC XY:

19485

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0906

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.298

Hom.:

1467

Bravo

AF:

0.259

Asia WGS

AF:

0.240

AC:

838

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 02, 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 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.39

DANN

Benign

0.82

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