NM_013351.2:c.491+2123G>A

Variant names:

• chr17-47736068-G-A
• rs16946264
• NM_013351.2:c.491+2123G>A

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+2123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,196 control chromosomes in the GnomAD database, including 1,029 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 0.11 (1029 hom., cov: 32)
• Consequence: TBX21 NM_013351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.99
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2	c.491+2123G>A		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+2123G>A		intron_variant	Intron 1 of 5	1	NM_013351.2	ENSP00000177694.1
TBX21	ENST00000581328.1	n.521+2123G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16857 AN: 152078 Hom.: 1031 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.111 AC: 16853 AN: 152196 Hom.: 1029 Cov.: 32 AF XY: 0.111 AC XY: 8228 AN XY: 74422

African (AFR) AF: 0.143 AC: 5954 AN: 41494

American (AMR) AF: 0.117 AC: 1797 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3468

East Asian (EAS) AF: 0.0573 AC: 297 AN: 5182

South Asian (SAS) AF: 0.193 AC: 931 AN: 4824

European-Finnish (FIN) AF: 0.0682 AC: 723 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6317 AN: 68002

Other (OTH) AF: 0.107 AC: 227 AN: 2116

Alfa AF: 0.0968 Hom.: 542

Bravo AF: 0.116

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.065
DANN	Benign	0.47
PhyloP100		-4.0
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: rs16946264; hg19: chr17-45813434;