Variant 18-658064-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001071.4(TYMS):c.205+117G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,571,972 control chromosomes in the GnomAD database, including 29,465 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 0.22 ( 4887 hom., cov: 33)

Exomes 𝑓: 0.16 ( 24578 hom. )

Consequence

TYMS
NM_001071.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.407

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]

TYMS links:

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

TYMSOS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TYMS	NM_001071.4 linkuse as main transcript	c.205+117G>C	intron_variant		ENST00000323274.15
TYMSOS	NR_171001.1 linkuse as main transcript	n.228C>G	non_coding_transcript_exon_variant	1/2
TYMS	NM_001354867.2 linkuse as main transcript	c.205+117G>C	intron_variant
TYMS	NM_001354868.2 linkuse as main transcript	c.205+117G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYMS	ENST00000323274.15 linkuse as main transcript	c.205+117G>C		intron_variant		1	NM_001071.4	P1	P04818-1
TYMSOS	ENST00000585033.1 linkuse as main transcript	n.206C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33786

AN:

152004

Hom.:

4879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.219

AC:

40867

AN:

186736

Hom.:

5892

AF XY:

0.219

AC XY:

22294

AN XY:

101772

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.535

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.164

AC:

233180

AN:

1419848

Hom.:

24578

Cov.:

AF XY:

0.168

AC XY:

118098

AN XY:

703284

show subpopulations

Gnomad4 AFR exome

AF:

0.377

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.222

AC:

33822

AN:

152124

Hom.:

4887

Cov.:

AF XY:

0.225

AC XY:

16705

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.529

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.158

Hom.:

774

Bravo

AF:

0.237

Asia WGS

AF:

0.428

AC:

1486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.3

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.33

Position offset: 3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over