rs11079788

Positions:

• chr17-47743357-C-T

Variant summary

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

The NM_013351.2(TBX21):​c.768+165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,012 control chromosomes in the GnomAD database, including 3,972 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 (3972 hom., cov: 31)
• Consequence: TBX21 NM_013351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX21	NM_013351.2	c.768+165C>T		intron_variant		ENST00000177694.2	NP_037483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2	c.768+165C>T		intron_variant		1	NM_013351.2	ENSP00000177694	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33899 AN: 151896 Hom.: 3970 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33915 AN: 152012 Hom.: 3972 Cov.: 31 AF XY: 0.221 AC XY: 16431 AN XY: 74288

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.220

Alfa AF: 0.235 Hom.: 470

Bravo AF: 0.219

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.9
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11079788; hg19: chr17-45820723;