rs112565029
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004608.4(TBX6):c.118+6C>T variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0287 in 1,584,626 control chromosomes in the GnomAD database, including 780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 45 hom., cov: 32)
Exomes 𝑓: 0.029 ( 735 hom. )
Consequence
TBX6
NM_004608.4 splice_donor_region, intron
NM_004608.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0003351
2
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
TBX6 (HGNC:11605): (T-box transcription factor 6) 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. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 16-30091070-G-A is Benign according to our data. Variant chr16-30091070-G-A is described in ClinVar as [Benign]. Clinvar id is 259447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30091070-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3456/152296) while in subpopulation NFE AF= 0.0348 (2365/67998). AF 95% confidence interval is 0.0336. There are 45 homozygotes in gnomad4. There are 1715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 45 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.118+6C>T | splice_donor_region_variant, intron_variant | ENST00000395224.7 | |||
TBX6 | XM_011545926.4 | c.118+6C>T | splice_donor_region_variant, intron_variant | ||||
TBX6 | XM_047434551.1 | c.118+6C>T | splice_donor_region_variant, intron_variant | ||||
TBX6 | XR_007064904.1 | n.241+6C>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.118+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_004608.4 | P1 | |||
TBX6 | ENST00000279386.6 | c.118+6C>T | splice_donor_region_variant, intron_variant | 1 | P1 | ||||
TBX6 | ENST00000553607.1 | c.118+6C>T | splice_donor_region_variant, intron_variant | 1 | |||||
TBX6 | ENST00000567664.5 | c.118+6C>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0227 AC: 3453AN: 152180Hom.: 45 Cov.: 32
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GnomAD3 exomes AF: 0.0225 AC: 4368AN: 194372Hom.: 72 AF XY: 0.0219 AC XY: 2295AN XY: 104810
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GnomAD4 exome AF: 0.0294 AC: 42040AN: 1432330Hom.: 735 Cov.: 31 AF XY: 0.0285 AC XY: 20236AN XY: 709820
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GnomAD4 genome ? AF: 0.0227 AC: 3456AN: 152296Hom.: 45 Cov.: 32 AF XY: 0.0230 AC XY: 1715AN XY: 74466
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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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at