NM_013351.2:c.491+813T>C

Variant names:

• chr17-47734758-T-C
• rs10514934
• NM_013351.2:c.491+813T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

TBX21 Gene-Disease associations (from GenCC):

• immunodeficiency 88

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBX21	NM_013351.2	c.491+813T>C		intron_variant	Intron 1 of 5	ENST00000177694.2	NP_037483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2	c.491+813T>C		intron_variant	Intron 1 of 5	1	NM_013351.2	ENSP00000177694.1
TBX21	ENST00000581328.1	n.521+813T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.0239 AC: 990 AN: 41400

American (AMR) AF: 0.0760 AC: 1159 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3466

East Asian (EAS) AF: 0.128 AC: 653 AN: 5116

South Asian (SAS) AF: 0.0693 AC: 331 AN: 4776

European-Finnish (FIN) AF: 0.157 AC: 1655 AN: 10534

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8779 AN: 67846

Other (OTH) AF: 0.105 AC: 221 AN: 2102

Alfa AF: 0.114 Hom.: 1374

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10514934; hg19: chr17-45812124;