rs10514934

Positions:

• chr17-47734758-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.491+813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 151,700 control chromosomes in the GnomAD database, including 860 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 0.094 (860 hom., cov: 29)
• Consequence: TBX21 NM_013351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX21	NM_013351.2	c.491+813T>C		intron_variant		ENST00000177694.2	NP_037483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2	c.491+813T>C		intron_variant		1	NM_013351.2	ENSP00000177694	P1
TBX21	ENST00000581328.1	n.521+813T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14229 AN: 151580 Hom.: 860 Cov.: 29

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0938 AC: 14233 AN: 151700 Hom.: 860 Cov.: 29 AF XY: 0.0938 AC XY: 6950 AN XY: 74122

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.105

Alfa AF: 0.120 Hom.: 1137

Bravo AF: 0.0864

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.51
DANN	Benign	0.64

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: rs10514934; hg19: chr17-45812124;