chr11-118339391-G-C

Variant names:

• chr11-118339391-G-C
• rs2276423
• NM_000732.6:c.450+60C>G

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 rank	MANE	Protein	UniProt
CD3D	NM_000732.6	c.450+60C>G		intron_variant	Intron 4 of 4	ENST00000300692.9	NP_000723.1
CD3D	NM_001040651.2	c.318+60C>G		intron_variant	Intron 3 of 3		NP_001035741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3D	ENST00000300692.9	c.450+60C>G		intron_variant	Intron 4 of 4	1	NM_000732.6	ENSP00000300692.4

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

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;