17-61455905-T-C
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001321120.2(TBX4):c.-3-583T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 152,180 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0062 ( 4 hom., cov: 33)
Consequence
TBX4
NM_001321120.2 intron
NM_001321120.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.969
Genes affected
TBX4 (HGNC:11603): (T-box transcription factor 4) 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 homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 17-61455905-T-C is Benign according to our data. Variant chr17-61455905-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647998.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00618 (940/152180) while in subpopulation NFE AF= 0.00956 (650/67984). AF 95% confidence interval is 0.00895. There are 4 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 940 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TBX4 | NM_001321120.2 | c.-3-583T>C | intron_variant | ENST00000644296.1 | NP_001308049.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TBX4 | ENST00000644296.1 | c.-3-583T>C | intron_variant | NM_001321120.2 | ENSP00000495986.1 | |||||
| TBX4 | ENST00000589003.5 | c.-125-719T>C | intron_variant | 3 | ENSP00000467588.1 |
Frequencies
GnomAD3 genomes 0.00618 AC: 940AN: 152062Hom.: 4 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00618 AC: 940AN: 152180Hom.: 4 Cov.: 33 AF XY: 0.00571 AC XY: 425AN XY: 74414
GnomAD4 genome
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TBX4: BS2 - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at