rs760471055
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BS1BS2
The NM_000474.4(TWIST1):c.260_274del(p.Ala87_Gly91del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000108 in 1,398,748 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 7 hom. )
Consequence
TWIST1
NM_000474.4 inframe_deletion
NM_000474.4 inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.49
Genes affected
TWIST1 (HGNC:12428): (twist family bHLH transcription factor 1) This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis, as well as metastatic recurrence. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM1
?
In a chain Twist-related protein 1 (size 201) in uniprot entity TWST1_HUMAN there are 59 pathogenic changes around while only 10 benign (86%) in NM_000474.4
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000307 (46/150060) while in subpopulation AFR AF= 0.00101 (42/41386). AF 95% confidence interval is 0.000771. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWIST1 | NM_000474.4 | c.260_274del | p.Ala87_Gly91del | inframe_deletion | 1/2 | ENST00000242261.6 | |
TWIST1 | NR_149001.2 | n.575_589del | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWIST1 | ENST00000242261.6 | c.260_274del | p.Ala87_Gly91del | inframe_deletion | 1/2 | 1 | NM_000474.4 | P1 | |
TWIST1 | ENST00000354571.5 | c.57_71del | p.Ala20_Gly24del | inframe_deletion, NMD_transcript_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000307 AC: 46AN: 149952Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000365 AC: 18AN: 49264Hom.: 4 AF XY: 0.000309 AC XY: 9AN XY: 29172
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GnomAD4 exome AF: 0.0000841 AC: 105AN: 1248688Hom.: 7 AF XY: 0.0000848 AC XY: 52AN XY: 613002
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GnomAD4 genome ? AF: 0.000307 AC: 46AN: 150060Hom.: 1 Cov.: 32 AF XY: 0.000232 AC XY: 17AN XY: 73240
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at