chr17-47733844-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013351.2(TBX21):​c.390A>G​(p.Gly130=) 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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.469
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1334938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-47733844-A-G is described in Lovd as [Benign].
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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TBX21NM_013351.2 linkuse as main transcriptc.390A>G p.Gly130= synonymous_variant 1/6 ENST00000177694.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBX21ENST00000177694.2 linkuse as main transcriptc.390A>G p.Gly130= synonymous_variant 1/61 NM_013351.2 P1
TBX21ENST00000581328.1 linkuse as main transcriptn.420A>G non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
AF:
0.282
AC:
42789
AN:
151746
Hom.:
6257
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.296
AC:
70657
AN:
238706
Hom.:
11079
AF XY:
0.298
AC XY:
38918
AN XY:
130754
show subpopulations
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 SAS exome
AF:
0.385
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
show subpopulations
Gnomad4 AFR exome
AF:
0.308
Gnomad4 AMR exome
AF:
0.389
Gnomad4 ASJ exome
AF:
0.288
Gnomad4 EAS exome
AF:
0.102
Gnomad4 SAS exome
AF:
0.379
Gnomad4 FIN exome
AF:
0.292
Gnomad4 NFE exome
AF:
0.262
Gnomad4 OTH exome
AF:
0.270
GnomAD4 genome
AF:
0.282
AC:
42805
AN:
151864
Hom.:
6253
Cov.:
32
AF XY:
0.284
AC XY:
21118
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.296
Gnomad4 AMR
AF:
0.321
Gnomad4 ASJ
AF:
0.289
Gnomad4 EAS
AF:
0.110
Gnomad4 SAS
AF:
0.386
Gnomad4 FIN
AF:
0.294
Gnomad4 NFE
AF:
0.268
Gnomad4 OTH
AF:
0.276
Alfa
AF:
0.255
Hom.:
3079
Bravo
AF:
0.285
Asia WGS
AF:
0.272
AC:
949
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -
Immunodeficiency 88 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
9.7
DANN
Benign
0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2074190; hg19: chr17-45811210; COSMIC: COSV51596223; API