rs2074190

Variant names:

• chr17-47733844-A-G
• rs2074190
• NM_013351.2:c.390A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-47733844-A-G
• chr17-47733844-A-C
• chr17-47733844-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013351.2(TBX21):​c.390A>G​(p.Gly130Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,609,696 control chromosomes in the GnomAD database, including 62,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6253 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55908 hom.)
• Consequence: TBX21 NM_013351.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.469
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-47733844-A-G is Benign according to our data. Variant chr17-47733844-A-G is described in ClinVar as Benign. ClinVar VariationId is 1334938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.469 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 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.390A>G	p.Gly130Gly	synonymous	Exon 1 of 6	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.390A>G	p.Gly130Gly	synonymous	Exon 1 of 6	ENSP00000177694.1	Q9UL17
	TBX21	ENST00000906368.1		c.390A>G	p.Gly130Gly	synonymous	Exon 1 of 7	ENSP00000576427.1
	TBX21	ENST00000581328.1	TSL:2	n.420A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42789 AN: 151746 Hom.: 6257 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.296 AC: 70657 AN: 238706 AF XY: 0.298

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.0982

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.272 AC: 395860 AN: 1457832 Hom.: 55908 Cov.: 35 AF XY: 0.274 AC XY: 198834 AN XY: 725092

African (AFR) AF: 0.308 AC: 10292 AN: 33434

American (AMR) AF: 0.389 AC: 17145 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7475 AN: 25998

East Asian (EAS) AF: 0.102 AC: 4042 AN: 39568

South Asian (SAS) AF: 0.379 AC: 32558 AN: 85936

European-Finnish (FIN) AF: 0.292 AC: 15267 AN: 52264

Middle Eastern (MID) AF: 0.334 AC: 1924 AN: 5768

European-Non Finnish (NFE) AF: 0.262 AC: 290919 AN: 1110578

Other (OTH) AF: 0.270 AC: 16238 AN: 60232

GnomAD4 genome AF: 0.282 AC: 42805 AN: 151864 Hom.: 6253 Cov.: 32 AF XY: 0.284 AC XY: 21118 AN XY: 74242

African (AFR) AF: 0.296 AC: 12263 AN: 41452

American (AMR) AF: 0.321 AC: 4910 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1004 AN: 3470

East Asian (EAS) AF: 0.110 AC: 560 AN: 5112

South Asian (SAS) AF: 0.386 AC: 1863 AN: 4824

European-Finnish (FIN) AF: 0.294 AC: 3106 AN: 10548

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18195 AN: 67878

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.257 Hom.: 3257

Bravo AF: 0.285

Asia WGS AF: 0.272 AC: 949 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 88 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.7
DANN	Benign	0.73
PhyloP100		0.47
Mutation Taster		=96/4	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: rs2074190; hg19: chr17-45811210; COSMIC: COSV51596223;