17-47744144-T-C

Variant names:

• chr17-47744144-T-C
• rs16946878
• NM_013351.2:c.769-51T>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.769-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,591,070 control chromosomes in the GnomAD database, including 2,179 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 0.055 (278 hom., cov: 31)
  • Exomes 𝑓: 0.049 (1901 hom.)
• Consequence: TBX21 NM_013351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2	c.769-51T>C		intron_variant	Intron 3 of 5	ENST00000177694.2	NP_037483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2	c.769-51T>C		intron_variant	Intron 3 of 5	1	NM_013351.2	ENSP00000177694.1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8346 AN: 151980 Hom.: 278 Cov.: 31

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0208

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0627

GnomAD2 exomes AF: 0.0443 AC: 10576 AN: 238784 AF XY: 0.0445

Gnomad AFR exome AF: 0.0780

Gnomad AMR exome AF: 0.0306

Gnomad ASJ exome AF: 0.0833

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0244

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0486 AC: 69892 AN: 1438972 Hom.: 1901 Cov.: 32 AF XY: 0.0481 AC XY: 34290 AN XY: 712726

African (AFR) AF: 0.0803 AC: 2657 AN: 33098

American (AMR) AF: 0.0333 AC: 1444 AN: 43396

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 2089 AN: 24736

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39368

South Asian (SAS) AF: 0.0234 AC: 1959 AN: 83560

European-Finnish (FIN) AF: 0.0256 AC: 1352 AN: 52710

Middle Eastern (MID) AF: 0.123 AC: 562 AN: 4578

European-Non Finnish (NFE) AF: 0.0517 AC: 56744 AN: 1098304

Other (OTH) AF: 0.0520 AC: 3080 AN: 59222

GnomAD4 genome AF: 0.0549 AC: 8344 AN: 152098 Hom.: 278 Cov.: 31 AF XY: 0.0515 AC XY: 3832 AN XY: 74362

African (AFR) AF: 0.0758 AC: 3143 AN: 41488

American (AMR) AF: 0.0431 AC: 659 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0906 AC: 314 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4812

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3743 AN: 67974

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0605 Hom.: 114

Bravo AF: 0.0595

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.35
PhyloP100		-2.5
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: rs16946878; hg19: chr17-45821510;