11-118339245-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000732.6(CD3D):c.451-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,608,916 control chromosomes in the GnomAD database, including 391,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30864 hom., cov: 30)

Exomes 𝑓: 0.70 ( 360835 hom. )

Consequence

CD3D
NM_000732.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.42

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-118339245-A-C is Benign according to our data. Variant chr11-118339245-A-C is described in ClinVar as [Benign]. Clinvar id is 518236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118339245-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD3D	NM_000732.6 linkuse as main transcript	c.451-18T>G		intron_variant		ENST00000300692.9
CD3D	NM_001040651.2 linkuse as main transcript	c.319-18T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD3D	ENST00000300692.9 linkuse as main transcript	c.451-18T>G		intron_variant		1	NM_000732.6	P1	P04234-1

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94379

AN:

151724

Hom.:

30874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.634

GnomAD3 exomes

AF:

0.671

AC:

168575

AN:

251394

Hom.:

58124

AF XY:

0.684

AC XY:

92894

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.718

Gnomad OTH exome

AF:

0.681

GnomAD4 exome

AF:

0.701

AC:

1020738

AN:

1457074

Hom.:

360835

Cov.:

AF XY:

0.703

AC XY:

509625

AN XY:

725184

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.492

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.759

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.713

Gnomad4 OTH exome

AF:

0.690

GnomAD4 genome

AF:

0.622

AC:

94393

AN:

151842

Hom.:

30864

Cov.:

AF XY:

0.625

AC XY:

46390

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.422

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.717

Gnomad4 FIN

AF:

0.721

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.632

Alfa

AF:

0.693

Hom.:

53087

Bravo

AF:

0.600

Asia WGS

AF:

0.738

AC:

2563

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Immunodeficiency 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Immunodeficiency 104

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

0.46

Dann

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over