rs2231449

Variant names:

• chr11-118315590-C-A
• rs2231449
• NM_000733.4:c.*48C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000733.4(CD3E):​c.*48C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,438,796 control chromosomes in the GnomAD database, including 588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (57 hom., cov: 30)
  • Exomes 𝑓: 0.026 (531 hom.)
• Consequence: CD3E NM_000733.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0990
• Publications: 8 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-118315590-C-A is Benign according to our data. Variant chr11-118315590-C-A is described in ClinVar as Benign. ClinVar VariationId is 302665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	NM_000733.4	MANE Select	c.*48C>A		3_prime_UTR	Exon 9 of 9	NP_000724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3E	ENST00000361763.9	TSL:1 MANE Select	c.*48C>A		3_prime_UTR	Exon 9 of 9	ENSP00000354566.4
	CD3E	ENST00000853938.1		c.*48C>A		3_prime_UTR	Exon 8 of 8	ENSP00000523997.1
	CD3E	ENST00000528600.1	TSL:5	c.*48C>A		3_prime_UTR	Exon 7 of 7	ENSP00000433975.1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3387 AN: 152020 Hom.: 58 Cov.: 30

Gnomad AFR AF: 0.00585

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0292 AC: 5404 AN: 185118 AF XY: 0.0273

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0633

Gnomad ASJ exome AF: 0.00475

Gnomad EAS exome AF: 0.0492

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0264

GnomAD4 exome AF: 0.0264 AC: 34015 AN: 1286658 Hom.: 531 Cov.: 20 AF XY: 0.0253 AC XY: 16288 AN XY: 642786

African (AFR) AF: 0.00430 AC: 128 AN: 29780

American (AMR) AF: 0.0599 AC: 2359 AN: 39402

Ashkenazi Jewish (ASJ) AF: 0.00535 AC: 131 AN: 24504

East Asian (EAS) AF: 0.0468 AC: 1727 AN: 36914

South Asian (SAS) AF: 0.00562 AC: 440 AN: 78314

European-Finnish (FIN) AF: 0.0171 AC: 857 AN: 50116

Middle Eastern (MID) AF: 0.00496 AC: 27 AN: 5446

European-Non Finnish (NFE) AF: 0.0281 AC: 27164 AN: 967912

Other (OTH) AF: 0.0218 AC: 1182 AN: 54270

GnomAD4 genome AF: 0.0222 AC: 3381 AN: 152138 Hom.: 57 Cov.: 30 AF XY: 0.0226 AC XY: 1680 AN XY: 74360

African (AFR) AF: 0.00583 AC: 242 AN: 41520

American (AMR) AF: 0.0579 AC: 884 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.0444 AC: 229 AN: 5156

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4816

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1781 AN: 67984

Other (OTH) AF: 0.0185 AC: 39 AN: 2110

Alfa AF: 0.0256 Hom.: 84

Bravo AF: 0.0239

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Immunodeficiency 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		-0.099
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2231449; hg19: chr11-118186305;