NM_000732.6:c.450+60C>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

CD3D Gene-Disease associations (from GenCC):

• immunodeficiency 19

  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=-0.9).
• BP6: Variant 11-118339391-G-C is Benign according to our data. Variant chr11-118339391-G-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000732.6. 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
	CD3D	NM_000732.6	MANE Select	c.450+60C>G		intron	N/A	NP_000723.1
	CD3D	NM_001040651.2		c.318+60C>G		intron	N/A	NP_001035741.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3D	ENST00000300692.9	TSL:1 MANE Select	c.450+60C>G		intron	N/A	ENSP00000300692.4
	CD3D	ENST00000529594.5	TSL:1	c.231+60C>G		intron	N/A	ENSP00000437335.1
	CD3D	ENST00000392884.3	TSL:2	c.318+60C>G		intron	N/A	ENSP00000376622.2

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

African (AFR) AF: 0.677 AC: 22295 AN: 32914

American (AMR) AF: 0.522 AC: 23346 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 19824 AN: 25974

East Asian (EAS) AF: 0.759 AC: 29996 AN: 39538

South Asian (SAS) AF: 0.718 AC: 61566 AN: 85720

European-Finnish (FIN) AF: 0.760 AC: 40574 AN: 53402

Middle Eastern (MID) AF: 0.739 AC: 4154 AN: 5622

European-Non Finnish (NFE) AF: 0.742 AC: 805580 AN: 1086120

Other (OTH) AF: 0.734 AC: 43645 AN: 59464

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

African (AFR) AF: 0.674 AC: 27873 AN: 41348

American (AMR) AF: 0.620 AC: 9458 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2668 AN: 3468

East Asian (EAS) AF: 0.771 AC: 3968 AN: 5148

South Asian (SAS) AF: 0.719 AC: 3468 AN: 4824

European-Finnish (FIN) AF: 0.753 AC: 7966 AN: 10576

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50402 AN: 67930

Other (OTH) AF: 0.701 AC: 1477 AN: 2106

Alfa AF: 0.726 Hom.: 5010

Bravo AF: 0.701

Asia WGS AF: 0.758 AC: 2632 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	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-0.76
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: rs2276423; hg19: chr11-118210106;