NM_000733.4:c.49+191G>A

Variant names:

• chr11-118305192-G-A
• rs57137348
• NM_000733.4:c.49+191G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000733.4(CD3E):​c.49+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 152,356 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0052 (9 hom., cov: 33)
• Consequence: CD3E NM_000733.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.73
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-118305192-G-A is Benign according to our data. Variant chr11-118305192-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1300877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00515 (785/152356) while in subpopulation AFR AF = 0.0179 (744/41574). AF 95% confidence interval is 0.0168. There are 9 homozygotes in GnomAd4. There are 364 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	NM_000733.4	MANE Select	c.49+191G>A		intron	N/A	NP_000724.1	P07766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	ENST00000361763.9	TSL:1 MANE Select	c.49+191G>A		intron	N/A	ENSP00000354566.4	P07766
	CD3E	ENST00000853938.1		c.49+191G>A		intron	N/A	ENSP00000523997.1
	CD3E	ENST00000528600.1	TSL:5	c.49+191G>A		intron	N/A	ENSP00000433975.1	E9PSH8

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 783 AN: 152238 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00515 AC: 785 AN: 152356 Hom.: 9 Cov.: 33 AF XY: 0.00489 AC XY: 364 AN XY: 74506

African (AFR) AF: 0.0179 AC: 744 AN: 41574

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.00563

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.041
DANN	Benign	0.67
PhyloP100		-4.7
PromoterAI		-0.042	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs57137348; hg19: chr11-118175907;