Variant chr11-118339391-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.757

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=-0.9).

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 link	c.450+60C>G		intron_variant	Intron 4 of 4	ENST00000300692.9	NP_000723.1	P04234-1B0YIY4
CD3D	NM_001040651.2 link	c.318+60C>G		intron_variant	Intron 3 of 3		NP_001035741.1	P04234-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3D	ENST00000300692.9 link	c.450+60C>G		intron_variant	Intron 4 of 4	1	NM_000732.6	ENSP00000300692.4		P04234-1

Frequencies

GnomAD3 genomes

AF:

0.713

AC:

108216

AN:

151738

Hom.:

38976

Cov.:

show subpopulations

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.:

AF XY:

0.734

AC XY:

524896

AN XY:

715120

show subpopulations

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.:

AF XY:

0.715

AC XY:

53044

AN XY:

74224

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

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