rs7502875

Variant names:

• chr17-47745861-A-C
• rs7502875
• NM_013351.2:c.*495A>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.*495A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 153,454 control chromosomes in the GnomAD database, including 3,970 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 0.22 (3940 hom., cov: 31)
  • Exomes 𝑓: 0.17 (30 hom.)
• Consequence: TBX21 NM_013351.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.*495A>C		3_prime_UTR	Exon 6 of 6	NP_037483.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	ENST00000177694.2	TSL:1 MANE Select	c.*495A>C		3_prime_UTR	Exon 6 of 6	ENSP00000177694.1
	TBX21	ENST00000906368.1		c.*495A>C		3_prime_UTR	Exon 7 of 7	ENSP00000576427.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33759 AN: 151790 Hom.: 3939 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.172 AC: 265 AN: 1544 Hom.: 30 Cov.: 0 AF XY: 0.172 AC XY: 132 AN XY: 766

African (AFR) AF: 0.300 AC: 3 AN: 10

American (AMR) AF: 0.120 AC: 35 AN: 292

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.111 AC: 8 AN: 72

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.190 AC: 206 AN: 1086

Other (OTH) AF: 0.203 AC: 13 AN: 64

GnomAD4 genome AF: 0.222 AC: 33777 AN: 151910 Hom.: 3940 Cov.: 31 AF XY: 0.220 AC XY: 16301 AN XY: 74254

African (AFR) AF: 0.248 AC: 10246 AN: 41384

American (AMR) AF: 0.178 AC: 2713 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3468

East Asian (EAS) AF: 0.0522 AC: 270 AN: 5172

South Asian (SAS) AF: 0.225 AC: 1079 AN: 4802

European-Finnish (FIN) AF: 0.225 AC: 2373 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15443 AN: 67950

Other (OTH) AF: 0.220 AC: 465 AN: 2114

Alfa AF: 0.226 Hom.: 16735

Bravo AF: 0.221

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.72
DANN	Benign	0.66
PhyloP100		-1.6
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: rs7502875; hg19: chr17-45823227;