rs2244500

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001071.4(TYMS):​c.280-1141A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

TYMS
NM_001071.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.903
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TYMSNM_001071.4 linkuse as main transcriptc.280-1141A>C intron_variant ENST00000323274.15
TYMSNM_001354867.2 linkuse as main transcriptc.280-1141A>C intron_variant
TYMSNM_001354868.2 linkuse as main transcriptc.205+3058A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TYMSENST00000323274.15 linkuse as main transcriptc.280-1141A>C intron_variant 1 NM_001071.4 P1P04818-1
TYMSENST00000323224.7 linkuse as main transcriptc.280-1141A>C intron_variant 1 P04818-2
TYMSENST00000323250.9 linkuse as main transcriptc.205+3058A>C intron_variant 1 P04818-3
TYMSENST00000579128.1 linkuse as main transcriptn.358-1141A>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.68
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2244500; hg19: chr18-661005; API