rs2606241

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000701410.1(TYMSOS):​n.154T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,974 control chromosomes in the GnomAD database, including 34,158 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 0.67 ( 34158 hom., cov: 30)

Consequence

TYMSOS
ENST00000701410.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.655
Variant links:
Genes affected
TYMSOS (HGNC:29553): (TYMS opposite strand RNA)
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=-0.89).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TYMSOSNR_171001.1 linkn.450+399T>G intron_variant Intron 1 of 1
TYMSNM_001071.4 linkc.-300A>C upstream_gene_variant ENST00000323274.15 NP_001062.1 P04818-1Q53Y97
TYMSNM_001354867.2 linkc.-300A>C upstream_gene_variant NP_001341796.1
TYMSNM_001354868.2 linkc.-300A>C upstream_gene_variant NP_001341797.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TYMSENST00000323274.15 linkc.-300A>C upstream_gene_variant 1 NM_001071.4 ENSP00000315644.10 P04818-1

Frequencies

GnomAD3 genomes
AF:
0.665
AC:
101030
AN:
151856
Hom.:
34123
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.543
Gnomad AMI
AF:
0.786
Gnomad AMR
AF:
0.726
Gnomad ASJ
AF:
0.724
Gnomad EAS
AF:
0.519
Gnomad SAS
AF:
0.651
Gnomad FIN
AF:
0.741
Gnomad MID
AF:
0.652
Gnomad NFE
AF:
0.721
Gnomad OTH
AF:
0.679
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.665
AC:
101115
AN:
151974
Hom.:
34158
Cov.:
30
AF XY:
0.668
AC XY:
49644
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.543
Gnomad4 AMR
AF:
0.726
Gnomad4 ASJ
AF:
0.724
Gnomad4 EAS
AF:
0.520
Gnomad4 SAS
AF:
0.650
Gnomad4 FIN
AF:
0.741
Gnomad4 NFE
AF:
0.721
Gnomad4 OTH
AF:
0.673
Alfa
AF:
0.604
Hom.:
2482
Bravo
AF:
0.657
Asia WGS
AF:
0.579
AC:
2012
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.97
DANN
Benign
0.47

Splicing

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: rs2606241; hg19: chr18-657443; API