rs17244587

chr17-47745669-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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=-0.88).
• 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/exons	MANE	UniProt
TBX21	NM_013351.2	c.*303G>A		3_prime_UTR_variant	6/6	ENST00000177694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX21	ENST00000177694.2	c.*303G>A		3_prime_UTR_variant	6/6	1	NM_013351.2	P1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12867 AN: 152106 Hom.: 604 Cov.: 32

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.: 2 AF XY: 0.0915 AC XY: 7193 AN XY: 78632

Gnomad4 AFR exome AF: 0.0634

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0790

Gnomad4 EAS exome AF: 0.0591

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.0827

Gnomad4 OTH exome AF: 0.0813

GnomAD4 genome AF: 0.0845 AC: 12867 AN: 152224 Hom.: 606 Cov.: 32 AF XY: 0.0866 AC XY: 6448 AN XY: 74442

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.0598

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.0793

Alfa AF: 0.0867 Hom.: 622

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
Dann	Benign	0.62

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: rs17244587; hg19: chr17-45823035;