rs2276423

Positions:

• chr11-118339391-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000732.6(CD3D):​c.450+60C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,585,296 control chromosomes in the GnomAD database, including 426,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38997 hom., cov: 29)
  • Exomes 𝑓: 0.73 (387059 hom.)
• Consequence: CD3D NM_000732.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.757

Genes affected

CD3D (HGNC:1673): (CD3 delta subunit of T-cell receptor complex) The protein encoded by this gene is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. The encoded membrane protein represents the delta subunit of the CD3 complex, and along with four other CD3 subunits, binds either TCR alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T-cells. Defects in this gene are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (SCIDBNK). Two transcript variants encoding different isoforms have been found for this gene. Other variants may also exist, but the full-length natures of their transcripts has yet to be defined. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-118339391-G-C is Benign according to our data. Variant chr11-118339391-G-C is described in ClinVar as [Benign]. Clinvar id is 1291549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD3D	NM_000732.6	c.450+60C>G		intron_variant		ENST00000300692.9	NP_000723.1
CD3D	NM_001040651.2	c.318+60C>G		intron_variant			NP_001035741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3D	ENST00000300692.9	c.450+60C>G		intron_variant		1	NM_000732.6	ENSP00000300692	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108216 AN: 151738 Hom.: 38976 Cov.: 29

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.733 AC: 1050980 AN: 1433442 Hom.: 387059 Cov.: 26 AF XY: 0.734 AC XY: 524896 AN XY: 715120

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.713 AC: 108273 AN: 151854 Hom.: 38997 Cov.: 29 AF XY: 0.715 AC XY: 53044 AN XY: 74224

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.701

Alfa AF: 0.726 Hom.: 5010

Bravo AF: 0.701

Asia WGS AF: 0.758 AC: 2632 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.47

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: rs2276423; hg19: chr11-118210106;