rs4819843

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000329705.11(TBX1):​c.1010-1561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,978 control chromosomes in the GnomAD database, including 2,766 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 0.19 ( 2766 hom., cov: 31)

Consequence

TBX1
ENST00000329705.11 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.595
Variant links:
Genes affected
TBX1 (HGNC:11592): (T-box transcription factor 1) 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 product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBX1NM_005992.1 linkuse as main transcriptc.1010-5254G>A intron_variant NP_005983.1
TBX1NM_080646.2 linkuse as main transcriptc.1010-1561G>A intron_variant NP_542377.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBX1ENST00000329705.11 linkuse as main transcriptc.1010-1561G>A intron_variant 1 ENSP00000331176 A2O43435-1
TBX1ENST00000359500.7 linkuse as main transcriptc.1010-5254G>A intron_variant 1 ENSP00000352483 A2O43435-2

Frequencies

GnomAD3 genomes
AF:
0.185
AC:
28130
AN:
151860
Hom.:
2759
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.136
Gnomad AMI
AF:
0.241
Gnomad AMR
AF:
0.232
Gnomad ASJ
AF:
0.200
Gnomad EAS
AF:
0.120
Gnomad SAS
AF:
0.366
Gnomad FIN
AF:
0.210
Gnomad MID
AF:
0.277
Gnomad NFE
AF:
0.191
Gnomad OTH
AF:
0.208
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.185
AC:
28160
AN:
151978
Hom.:
2766
Cov.:
31
AF XY:
0.190
AC XY:
14107
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.136
Gnomad4 AMR
AF:
0.233
Gnomad4 ASJ
AF:
0.200
Gnomad4 EAS
AF:
0.120
Gnomad4 SAS
AF:
0.364
Gnomad4 FIN
AF:
0.210
Gnomad4 NFE
AF:
0.191
Gnomad4 OTH
AF:
0.209
Alfa
AF:
0.181
Hom.:
1539
Bravo
AF:
0.184
Asia WGS
AF:
0.242
AC:
842
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.95
DANN
Benign
0.64

Splicing

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: rs4819843; hg19: chr22-19765182; API