rs7502875

chr17-47745861-A-C

Variant summary

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

The NM_013351.2(TBX21):c.*495A>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 0.222 in 153,454 control chromosomes in the GnomAD database, including 3,970 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 0.22 (3940 hom., cov: 31)
  • Exomes 𝑓: 0.17 (30 hom.)
• Consequence: TBX21 NM_013351.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX21	NM_013351.2	c.*495A>C		3_prime_UTR_variant	6/6	ENST00000177694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX21	ENST00000177694.2	c.*495A>C		3_prime_UTR_variant	6/6	1	NM_013351.2	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33759 AN: 151790 Hom.: 3939 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.172 AC: 265 AN: 1544 Hom.: 30 Cov.: 0 AF XY: 0.172 AC XY: 132 AN XY: 766

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.120

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.222 AC: 33777 AN: 151910 Hom.: 3940 Cov.: 31 AF XY: 0.220 AC XY: 16301 AN XY: 74254

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.220

Alfa AF: 0.230 Hom.: 8162

Bravo AF: 0.221

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.72
Dann	Benign	0.66

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: rs7502875; hg19: chr17-45823227;