dbSNP rs17244587: TBX21:c.*303G>A (chr17-47745669-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_013351.2(TBX21):c.*303G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 306,452 control chromosomes in the GnomAD database, including 1,359 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 0.085 ( 606 hom., cov: 32)

Exomes 𝑓: 0.088 ( 753 hom. )

Consequence

TBX21
NM_013351.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0230

Publications

15 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2 link	c.*303G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000177694.2	NP_037483.1	Q9UL17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2 link	c.*303G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_013351.2	ENSP00000177694.1		Q9UL17

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12867

AN:

152106

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0664

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0864

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.0738

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0885

Gnomad OTH

AF:

0.0797

GnomAD4 exome

AF:

0.0880

AC:

13567

AN:

154228

Hom.:

753

Cov.:

AF XY:

0.0915

AC XY:

7193

AN XY:

78632

show subpopulations

African (AFR)

AF:

0.0634

AC:

323

AN:

5094

American (AMR)

AF:

0.123

AC:

777

AN:

6306

Ashkenazi Jewish (ASJ)

AF:

0.0790

AC:

424

AN:

5370

East Asian (EAS)

AF:

0.0591

AC:

645

AN:

10910

South Asian (SAS)

AF:

0.192

AC:

1830

AN:

9550

European-Finnish (FIN)

AF:

0.0741

AC:

591

AN:

7972

Middle Eastern (MID)

AF:

0.0455

AC:

AN:

704

European-Non Finnish (NFE)

AF:

0.0827

AC:

8173

AN:

98832

Other (OTH)

AF:

0.0813

AC:

772

AN:

9490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

589

1178

1768

2357

2946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.0845

AC:

12867

AN:

152224

Hom.:

606

Cov.:

AF XY:

0.0866

AC XY:

6448

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0663

AC:

2756

AN:

41542

American (AMR)

AF:

0.0970

AC:

1483

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0864

AC:

300

AN:

3472

East Asian (EAS)

AF:

0.0598

AC:

310

AN:

5188

South Asian (SAS)

AF:

0.206

AC:

992

AN:

4818

European-Finnish (FIN)

AF:

0.0738

AC:

783

AN:

10606

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0885

AC:

6017

AN:

67992

Other (OTH)

AF:

0.0793

AC:

167

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

595

1190

1785

2380

2975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0863

Hom.:

1687

Bravo

AF:

0.0832

Asia WGS

AF:

0.133

AC:

466

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

1.5

(source)

DANN

Benign

0.62

PhyloP100

0.023

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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