17-47744726-C-T

Position:

• chr17-47744726-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.990-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,601,660 control chromosomes in the GnomAD database, including 23,100 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 0.15 (1933 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21167 hom.)
• Consequence: TBX21 NM_013351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX21	NM_013351.2	c.990-22C>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.990-22C>T		intron_variant		1	NM_013351.2	ENSP00000177694.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23353 AN: 151920 Hom.: 1935 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.156 AC: 38286 AN: 245038 Hom.: 3263 AF XY: 0.161 AC XY: 21366 AN XY: 132458

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.0448

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.167 AC: 241970 AN: 1449620 Hom.: 21167 Cov.: 33 AF XY: 0.168 AC XY: 120660 AN XY: 719576

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0396

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.154 AC: 23353 AN: 152040 Hom.: 1933 Cov.: 31 AF XY: 0.155 AC XY: 11545 AN XY: 74294

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.147

Alfa AF: 0.172 Hom.: 3174

Bravo AF: 0.144

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.75

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: rs11650354; hg19: chr17-45822092; COSMIC: COSV51596336; COSMIC: COSV51596336;