rs11171846
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_003920.5(TIMELESS):c.-61-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 936,264 control chromosomes in the GnomAD database, including 3,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.064 ( 427 hom., cov: 32)
Exomes 𝑓: 0.076 ( 2823 hom. )
Consequence
TIMELESS
NM_003920.5 intron
NM_003920.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.508
Genes affected
TIMELESS (HGNC:11813): (timeless circadian regulator) The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]
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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=-0.76).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMELESS | NM_003920.5 | c.-61-41G>A | intron_variant | ENST00000553532.6 | |||
TIMELESS | NM_001330295.2 | c.-61-41G>A | intron_variant | ||||
TIMELESS | NR_138471.2 | n.118-41G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMELESS | ENST00000553532.6 | c.-61-41G>A | intron_variant | 1 | NM_003920.5 | P4 | |||
TIMELESS | ENST00000229201.4 | c.-61-41G>A | intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0641 AC: 9753AN: 152104Hom.: 428 Cov.: 32
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GnomAD4 exome AF: 0.0764 AC: 59929AN: 784042Hom.: 2823 Cov.: 10 AF XY: 0.0757 AC XY: 30990AN XY: 409506
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GnomAD4 genome ? AF: 0.0640 AC: 9743AN: 152222Hom.: 427 Cov.: 32 AF XY: 0.0620 AC XY: 4612AN XY: 74418
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ClinVar
Not reported inComputational 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