dbSNP rs1561966: CD3G:c.439+76G>A (chr11-118350759-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000073.3(CD3G):c.439+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,607,790 control chromosomes in the GnomAD database, including 88,238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8141 hom., cov: 28)

Exomes 𝑓: 0.32 ( 80097 hom. )

Consequence

CD3G
NM_000073.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.183

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

combined immunodeficiency due to CD3gamma deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

CD3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3 link	c.439+76G>A		intron_variant	Intron 4 of 6	ENST00000532917.3	NP_000064.1	P09693B0YIY5
CD3G	XM_005271724.5 link	c.515G>A	p.Trp172*	stop_gained	Exon 4 of 4		XP_005271781.1
CD3G	NM_001440319.1 link	c.439+76G>A		intron_variant	Intron 4 of 6		NP_001427248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3 link	c.439+76G>A		intron_variant	Intron 4 of 6	1	NM_000073.3	ENSP00000431445.2		P09693

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48505

AN:

151050

Hom.:

8135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.323

AC:

470114

AN:

1456622

Hom.:

80097

Cov.:

AF XY:

0.329

AC XY:

238467

AN XY:

724684

show subpopulations

African (AFR)

AF:

0.324

AC:

10820

AN:

33388

American (AMR)

AF:

0.207

AC:

9221

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9205

AN:

26012

East Asian (EAS)

AF:

0.580

AC:

22855

AN:

39398

South Asian (SAS)

AF:

0.520

AC:

44681

AN:

85890

European-Finnish (FIN)

AF:

0.305

AC:

15837

AN:

51946

Middle Eastern (MID)

AF:

0.328

AC:

1693

AN:

5160

European-Non Finnish (NFE)

AF:

0.302

AC:

335450

AN:

1110108

Other (OTH)

AF:

0.339

AC:

20352

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14613

29226

43840

58453

73066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11328

22656

33984

45312

56640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48552

AN:

151168

Hom.:

8141

Cov.:

AF XY:

0.328

AC XY:

24197

AN XY:

73846

show subpopulations

African (AFR)

AF:

0.325

AC:

13356

AN:

41120

American (AMR)

AF:

0.253

AC:

3839

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1200

AN:

3456

East Asian (EAS)

AF:

0.577

AC:

2952

AN:

5114

South Asian (SAS)

AF:

0.526

AC:

2487

AN:

4728

European-Finnish (FIN)

AF:

0.320

AC:

3354

AN:

10474

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.302

AC:

20473

AN:

67784

Other (OTH)

AF:

0.299

AC:

631

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.306

Hom.:

12345

Bravo

AF:

0.313

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

(source)

DANN

Benign

0.40

PhyloP100

0.18

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over