dbSNP rs11657479: TBX21:c.*169T>C (chr17-47745535-T-C) – 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.*169T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 906,968 control chromosomes in the GnomAD database, including 22,948 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 0.20 ( 3299 hom., cov: 32)

Exomes 𝑓: 0.22 ( 19649 hom. )

Consequence

TBX21
NM_013351.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

20 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=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2 link	c.*169T>C		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.*169T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_013351.2	ENSP00000177694.1		Q9UL17

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30142

AN:

152016

Hom.:

3303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.0512

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.220

AC:

166399

AN:

754832

Hom.:

19649

Cov.:

AF XY:

0.220

AC XY:

83475

AN XY:

379354

show subpopulations

African (AFR)

AF:

0.136

AC:

2497

AN:

18348

American (AMR)

AF:

0.158

AC:

2612

AN:

16482

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

3790

AN:

15398

East Asian (EAS)

AF:

0.0385

AC:

1230

AN:

31966

South Asian (SAS)

AF:

0.205

AC:

9678

AN:

47314

European-Finnish (FIN)

AF:

0.249

AC:

7358

AN:

29504

Middle Eastern (MID)

AF:

0.281

AC:

729

AN:

2590

European-Non Finnish (NFE)

AF:

0.235

AC:

130858

AN:

557468

Other (OTH)

AF:

0.214

AC:

7647

AN:

35762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

6140

12280

18420

24560

30700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3388

6776

10164

13552

16940

<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:

0.198

AC:

30143

AN:

152136

Hom.:

3299

Cov.:

AF XY:

0.197

AC XY:

14681

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.134

AC:

5579

AN:

41502

American (AMR)

AF:

0.179

AC:

2735

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

859

AN:

3472

East Asian (EAS)

AF:

0.0515

AC:

266

AN:

5170

South Asian (SAS)

AF:

0.219

AC:

1057

AN:

4818

European-Finnish (FIN)

AF:

0.250

AC:

2646

AN:

10582

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16273

AN:

67986

Other (OTH)

AF:

0.204

AC:

431

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1196

2392

3587

4783

5979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.232

Hom.:

5734

Bravo

AF:

0.190

Asia WGS

AF:

0.146

AC:

510

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.9

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