Genetic Variant CD3G:c.-46_-43delGCTG (chr11-118344360-AGGCT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000073.3(CD3G):c.-46_-43delGCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,387,408 control chromosomes in the GnomAD database, including 72,888 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8033 hom., cov: 0)

Exomes 𝑓: 0.31 ( 64855 hom. )

Consequence

CD3G
NM_000073.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

CD3G (HGNC:1675): (CD3 gamma subunit of T-cell receptor complex) The protein encoded by this gene is the CD3-gamma polypeptide, which together with CD3-epsilon, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. Defects in this gene are associated with T cell immunodeficiency. [provided by RefSeq, Jul 2008]

CD3G links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-118344360-AGGCT-A is Benign according to our data. Variant chr11-118344360-AGGCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 302678.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3 link	c.-46_-43delGCTG	5_prime_UTR_variant	Exon 1 of 7	ENST00000532917.3	NP_000064.1	P09693B0YIY5
CD3G	NM_001440319.1 link	c.-46_-43delGCTG	5_prime_UTR_variant	Exon 1 of 7
CD3G	XM_005271724.5 link	c.-46_-43delGCTG	5_prime_UTR_variant	Exon 1 of 4		XP_005271781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3 link	c.-46_-43delGCTG		5_prime_UTR_variant	Exon 1 of 7	1	NM_000073.3	ENSP00000431445.2		P09693

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48484

AN:

151670

Hom.:

8026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.290

GnomAD4 exome

AF:

0.311

AC:

384148

AN:

1235620

Hom.:

64855

AF XY:

0.318

AC XY:

196522

AN XY:

617050

show subpopulations

African (AFR)

AF:

0.322

AC:

9156

AN:

28438

American (AMR)

AF:

0.208

AC:

7385

AN:

35492

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

8485

AN:

24088

East Asian (EAS)

AF:

0.556

AC:

19338

AN:

34808

South Asian (SAS)

AF:

0.513

AC:

38716

AN:

75508

European-Finnish (FIN)

AF:

0.305

AC:

14891

AN:

48816

Middle Eastern (MID)

AF:

0.319

AC:

1648

AN:

5160

European-Non Finnish (NFE)

AF:

0.287

AC:

267469

AN:

930896

Other (OTH)

AF:

0.325

AC:

17060

AN:

52414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

13111

26221

39332

52442

65553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.320

AC:

48534

AN:

151788

Hom.:

8033

Cov.:

AF XY:

0.326

AC XY:

24172

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.330

AC:

13661

AN:

41410

American (AMR)

AF:

0.251

AC:

3827

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.550

AC:

2810

AN:

5110

South Asian (SAS)

AF:

0.522

AC:

2510

AN:

4806

European-Finnish (FIN)

AF:

0.318

AC:

3348

AN:

10536

Middle Eastern (MID)

AF:

0.288

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.299

AC:

20308

AN:

67894

Other (OTH)

AF:

0.292

AC:

614

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1608

3216

4823

6431

8039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.176

Hom.:

333

Bravo

AF:

0.311

Asia WGS

AF:

0.518

AC:

1801

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency due to defect in CD3-gamma

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe combined immunodeficiency disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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11-118344360-AGGCT-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over