17-47733844-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013351.2(TBX21):c.390A>G(p.Gly130Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,609,696 control chromosomes in the GnomAD database, including 62,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6253 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55908 hom. )

Consequence

TBX21
NM_013351.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.469

Publications

25 publications found

Variant links:

Genes affected

TBX21 (HGNC:11599): (T-box transcription factor 21) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human ortholog of mouse Tbx21/Tbet gene. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (IFNG). Expression of the human ortholog also correlates with IFNG expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells. [provided by RefSeq, Jul 2008]

TBX21 Gene-Disease associations (from GenCC):

immunodeficiency 88
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TBX21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-47733844-A-G is Benign according to our data. Variant chr17-47733844-A-G is described in ClinVar as Benign. ClinVar VariationId is 1334938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.469 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	NM_013351.2	MANE Select	c.390A>G	p.Gly130Gly	synonymous	Exon 1 of 6	NP_037483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	ENST00000177694.2	TSL:1 MANE Select	c.390A>G	p.Gly130Gly	synonymous	Exon 1 of 6	ENSP00000177694.1
	TBX21	ENST00000581328.1	TSL:2	n.420A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42789

AN:

151746

Hom.:

6257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.296

AC:

70657

AN:

238706

AF XY:

0.298

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.0982

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.272

AC:

395860

AN:

1457832

Hom.:

55908

Cov.:

AF XY:

0.274

AC XY:

198834

AN XY:

725092

show subpopulations

African (AFR)

AF:

0.308

AC:

10292

AN:

33434

American (AMR)

AF:

0.389

AC:

17145

AN:

44054

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

7475

AN:

25998

East Asian (EAS)

AF:

0.102

AC:

4042

AN:

39568

South Asian (SAS)

AF:

0.379

AC:

32558

AN:

85936

European-Finnish (FIN)

AF:

0.292

AC:

15267

AN:

52264

Middle Eastern (MID)

AF:

0.334

AC:

1924

AN:

5768

European-Non Finnish (NFE)

AF:

0.262

AC:

290919

AN:

1110578

Other (OTH)

AF:

0.270

AC:

16238

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

18740

37480

56221

74961

93701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9834

19668

29502

39336

49170

<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:

0.282

AC:

42805

AN:

151864

Hom.:

6253

Cov.:

AF XY:

0.284

AC XY:

21118

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.296

AC:

12263

AN:

41452

American (AMR)

AF:

0.321

AC:

4910

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1004

AN:

3470

East Asian (EAS)

AF:

0.110

AC:

560

AN:

5112

South Asian (SAS)

AF:

0.386

AC:

1863

AN:

4824

European-Finnish (FIN)

AF:

0.294

AC:

3106

AN:

10548

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.268

AC:

18195

AN:

67878

Other (OTH)

AF:

0.276

AC:

582

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1610

3219

4829

6438

8048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.257

Hom.:

3257

Bravo

AF:

0.285

Asia WGS

AF:

0.272

AC:

949

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported.

Immunodeficiency 88

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.7

(source)

DANN

Benign

0.73

PhyloP100

0.47

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over