11-118315204-A-G

Position:

• chr11-118315204-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD3E	NM_000733.4	c.568-282A>G		intron_variant		ENST00000361763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD3E	ENST00000361763.9	c.568-282A>G		intron_variant		1	NM_000733.4	P1
CD3E	ENST00000528600.1	c.550-282A>G		intron_variant		5
CD3E	ENST00000526146.5	n.1954-282A>G		intron_variant, non_coding_transcript_variant		2
CD3E	ENST00000531913.1	n.939-282A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.543

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

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	-0.89
CADD	Benign	2.2
DANN	Benign	0.31

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: rs3782042; hg19: chr11-118185919;