rs112978646

Variant names:

• chr11-118307208-C-A
• rs112978646
• NM_000733.4:c.50-80C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-118307208-C-A
• chr11-118307208-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000733.4(CD3E):​c.50-80C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,102,140 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (46 hom.)
• Consequence: CD3E NM_000733.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.147
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-118307208-C-A is Benign according to our data. Variant chr11-118307208-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1321578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2051/152244) while in subpopulation AFR AF = 0.0476 (1975/41522). AF 95% confidence interval is 0.0458. There are 47 homozygotes in GnomAd4. There are 963 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 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.50-80C>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.50-80C>A		intron	N/A	ENSP00000354566.4	P07766
	CD3E	ENST00000853938.1		c.50-80C>A		intron	N/A	ENSP00000523997.1
	CD3E	ENST00000528600.1	TSL:5	c.50-80C>A		intron	N/A	ENSP00000433975.1	E9PSH8

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2039 AN: 152126 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00163 AC: 1548 AN: 949896 Hom.: 46 AF XY: 0.00133 AC XY: 656 AN XY: 493104

African (AFR) AF: 0.0501 AC: 1199 AN: 23952

American (AMR) AF: 0.00289 AC: 117 AN: 40532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22452

East Asian (EAS) AF: 0.00 AC: 0 AN: 37396

South Asian (SAS) AF: 0.000246 AC: 18 AN: 73246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52410

Middle Eastern (MID) AF: 0.00357 AC: 17 AN: 4764

European-Non Finnish (NFE) AF: 0.0000337 AC: 22 AN: 651872

Other (OTH) AF: 0.00404 AC: 175 AN: 43272

GnomAD4 genome AF: 0.0135 AC: 2051 AN: 152244 Hom.: 47 Cov.: 31 AF XY: 0.0129 AC XY: 963 AN XY: 74440

African (AFR) AF: 0.0476 AC: 1975 AN: 41522

American (AMR) AF: 0.00333 AC: 51 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00603 Hom.: 7

Bravo AF: 0.0155

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.15
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: rs112978646; hg19: chr11-118177923;