22-19759641-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000332710.8(TBX1):c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,612,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
TBX1
ENST00000332710.8 5_prime_UTR
ENST00000332710.8 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.52
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 22-19759641-G-A is Benign according to our data. Variant chr22-19759641-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 389277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00105 (160/152380) while in subpopulation AFR AF= 0.00373 (155/41594). AF 95% confidence interval is 0.00325. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 160 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_005992.1 | c.-3G>A | 5_prime_UTR_variant | 2/10 | |||
TBX1 | NM_080646.2 | c.-3G>A | 5_prime_UTR_variant | 2/9 | |||
TBX1 | NM_080647.1 | c.-3G>A | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000329705.11 | c.-3G>A | 5_prime_UTR_variant | 2/9 | 1 | A2 | |||
TBX1 | ENST00000332710.8 | c.-3G>A | 5_prime_UTR_variant | 2/9 | 1 | P2 | |||
TBX1 | ENST00000359500.7 | c.-3G>A | 5_prime_UTR_variant | 2/10 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 160AN: 152262Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
160
AN:
152262
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000260 AC: 64AN: 246592Hom.: 0 AF XY: 0.000201 AC XY: 27AN XY: 134244
GnomAD3 exomes
AF:
AC:
64
AN:
246592
Hom.:
AF XY:
AC XY:
27
AN XY:
134244
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000101 AC: 147AN: 1460034Hom.: 0 Cov.: 34 AF XY: 0.0000950 AC XY: 69AN XY: 726308
GnomAD4 exome
AF:
AC:
147
AN:
1460034
Hom.:
Cov.:
34
AF XY:
AC XY:
69
AN XY:
726308
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00105 AC: 160AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68AN XY: 74520
GnomAD4 genome
?
AF:
AC:
160
AN:
152380
Hom.:
Cov.:
33
AF XY:
AC XY:
68
AN XY:
74520
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2022 | See Variant Classification Assertion Criteria. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at