Genetic Variant NM_013351.2:c.*495A>C (chr17-47745861-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

15 publications found

Variant links:

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)

TBX21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2 link	c.*495A>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000177694.2	NP_037483.1	Q9UL17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2 link	c.*495A>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_013351.2	ENSP00000177694.1		Q9UL17

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33759

AN:

151790

Hom.:

3939

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.172

AC XY:

132

AN XY:

766

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.120

AC:

AN:

292

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.111

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.190

AC:

206

AN:

1086

Other (OTH)

AF:

0.203

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33777

AN:

151910

Hom.:

3940

Cov.:

AF XY:

0.220

AC XY:

16301

AN XY:

74254

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15443

AN:

67950

Other (OTH)

AF:

0.220

AC:

465

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1309

2618

3928

5237

6546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.72

(source)

DANN

Benign

0.66

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over