rs1004474
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001071.4(TYMS):c.279+669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,062 control chromosomes in the GnomAD database, including 20,193 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 0.51 ( 20193 hom., cov: 32)
Consequence
TYMS
NM_001071.4 intron
NM_001071.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.31
Genes affected
TYMS (HGNC:12441): (thymidylate synthetase) Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]
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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=-0.9).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMS | NM_001071.4 | c.279+669A>G | intron_variant | ENST00000323274.15 | |||
TYMS | NM_001354867.2 | c.279+669A>G | intron_variant | ||||
TYMS | NM_001354868.2 | c.205+2436A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMS | ENST00000323274.15 | c.279+669A>G | intron_variant | 1 | NM_001071.4 | P1 | |||
TYMS | ENST00000323224.7 | c.279+669A>G | intron_variant | 1 | |||||
TYMS | ENST00000323250.9 | c.205+2436A>G | intron_variant | 1 | |||||
TYMS | ENST00000579128.1 | n.357+669A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.505 AC: 76750AN: 151944Hom.: 20170 Cov.: 32
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.505 AC: 76810AN: 152062Hom.: 20193 Cov.: 32 AF XY: 0.502 AC XY: 37302AN XY: 74330
GnomAD4 genome
?
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37302
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1815
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at