chr22-19759510-C-G
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The ENST00000332710.8(TBX1):c.-86-48C>G variant causes a intron change. The variant allele was found at a frequency of 0.0135 in 1,514,532 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0079 ( 11 hom., cov: 35)
Exomes 𝑓: 0.014 ( 171 hom. )
Consequence
TBX1
ENST00000332710.8 intron
ENST00000332710.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.22
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
Variant 22-19759510-C-G is Benign according to our data. Variant chr22-19759510-C-G is described in ClinVar as [Benign]. Clinvar id is 2652866.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00787 (1199/152340) while in subpopulation NFE AF= 0.0143 (970/68022). AF 95% confidence interval is 0.0135. There are 11 homozygotes in gnomad4. There are 523 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1200 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_005992.1 | c.-86-48C>G | intron_variant | ||||
TBX1 | NM_080646.2 | c.-86-48C>G | intron_variant | ||||
TBX1 | NM_080647.1 | c.-86-48C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000329705.11 | c.-86-48C>G | intron_variant | 1 | A2 | ||||
TBX1 | ENST00000332710.8 | c.-86-48C>G | intron_variant | 1 | P2 | ||||
TBX1 | ENST00000359500.7 | c.-86-48C>G | intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00788 AC: 1200AN: 152222Hom.: 11 Cov.: 35
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GnomAD4 exome AF: 0.0141 AC: 19215AN: 1362192Hom.: 171 Cov.: 29 AF XY: 0.0136 AC XY: 9105AN XY: 670452
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GnomAD4 genome ? AF: 0.00787 AC: 1199AN: 152340Hom.: 11 Cov.: 35 AF XY: 0.00702 AC XY: 523AN XY: 74496
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TBX1: BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at