11-118304825-A-G

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.-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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.686

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=-0.7).
• 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/exons	MANE	UniProt
CD3E	NM_000733.4	c.-60+49A>G		intron_variant		ENST00000361763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD3E	ENST00000361763.9	c.-60+49A>G		intron_variant		1	NM_000733.4	P1
CD3E	ENST00000526146.5	n.40+49A>G		intron_variant, non_coding_transcript_variant		2
CD3E	ENST00000528435.5	n.47+49A>G		intron_variant, non_coding_transcript_variant		2
CD3E	ENST00000529713.5	n.47+49A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39508 AN: 152078 Hom.: 6184 Cov.: 33

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.: 8 AF XY: 0.315 AC XY: 113762 AN XY: 361150

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.: 33 AF XY: 0.262 AC XY: 19485 AN XY: 74394

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2018

- -

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

Other links and lift over

dbSNP: rs2231441; hg19: chr11-118175540; COSMIC: COSV62346624; COSMIC: COSV62346624;