rs11657479

Positions:

• chr17-47745535-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TBX21	NM_013351.2	c.*169T>C		3_prime_UTR_variant	6/6	ENST00000177694.2	NP_037483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2	c.*169T>C		3_prime_UTR_variant	6/6	1	NM_013351.2	ENSP00000177694	P1

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

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.214

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.204

Alfa AF: 0.240 Hom.: 4200

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	13
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs11657479; hg19: chr17-45822901;