rs11657479

Variant names:

• chr17-47745535-T-C
• rs11657479
• NM_013351.2:c.*169T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 20 publications found

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):

• asthma, nasal polyps, and aspirin intolerance

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia
• immunodeficiency 88

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	NM_013351.2	MANE Select	c.*169T>C		3_prime_UTR	Exon 6 of 6	NP_037483.1	Q9UL17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	ENST00000177694.2	TSL:1 MANE Select	c.*169T>C		3_prime_UTR	Exon 6 of 6	ENSP00000177694.1	Q9UL17
	TBX21	ENST00000906368.1		c.*169T>C		3_prime_UTR	Exon 7 of 7	ENSP00000576427.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30142 AN: 152016 Hom.: 3303 Cov.: 32

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.: 10 AF XY: 0.220 AC XY: 83475 AN XY: 379354

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

GnomAD4 genome AF: 0.198 AC: 30143 AN: 152136 Hom.: 3299 Cov.: 32 AF XY: 0.197 AC XY: 14681 AN XY: 74372

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: 95 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16273 AN: 67986

Other (OTH) AF: 0.204 AC: 431 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11657479; hg19: chr17-45822901;