17-47744726-C-T

Variant names:

• chr17-47744726-C-T
• rs11650354
• NM_013351.2:c.990-22C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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):

• asthma, nasal polyps, and aspirin intolerance

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia
• immunodeficiency 88

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	NM_013351.2	MANE Select	c.990-22C>T		intron	N/A	NP_037483.1	Q9UL17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	ENST00000177694.2	TSL:1 MANE Select	c.990-22C>T		intron	N/A	ENSP00000177694.1	Q9UL17
	TBX21	ENST00000906368.1		c.1053-22C>T		intron	N/A	ENSP00000576427.1

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

GnomAD2 exomes AF: 0.156 AC: 38286 AN: 245038 AF XY: 0.161

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 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

African (AFR) AF: 0.120 AC: 3973 AN: 33076

American (AMR) AF: 0.105 AC: 4589 AN: 43748

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3454 AN: 25374

East Asian (EAS) AF: 0.0396 AC: 1564 AN: 39522

South Asian (SAS) AF: 0.181 AC: 15413 AN: 85182

European-Finnish (FIN) AF: 0.223 AC: 11826 AN: 53134

Middle Eastern (MID) AF: 0.141 AC: 805 AN: 5690

European-Non Finnish (NFE) AF: 0.173 AC: 191038 AN: 1104154

Other (OTH) AF: 0.156 AC: 9308 AN: 59740

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

African (AFR) AF: 0.117 AC: 4864 AN: 41498

American (AMR) AF: 0.132 AC: 2011 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3464

East Asian (EAS) AF: 0.0503 AC: 260 AN: 5172

South Asian (SAS) AF: 0.194 AC: 934 AN: 4808

European-Finnish (FIN) AF: 0.227 AC: 2394 AN: 10546

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11893 AN: 67958

Other (OTH) AF: 0.147 AC: 310 AN: 2108

Alfa AF: 0.169 Hom.: 3872

Bravo AF: 0.144

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		-1.2
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: rs11650354; hg19: chr17-45822092; COSMIC: COSV51596336; COSMIC: COSV51596336;