rs2853533

Variant names:

• chr18-658064-G-C
• rs2853533
• NM_001071.4:c.205+117G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-658064-G-C
• chr18-658064-G-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

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]

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

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYMS	NM_001071.4	c.205+117G>C		intron_variant	Intron 1 of 6	ENST00000323274.15	NP_001062.1
TYMS	NM_001354867.2	c.205+117G>C		intron_variant	Intron 1 of 5		NP_001341796.1
TYMS	NM_001354868.2	c.205+117G>C		intron_variant	Intron 1 of 4		NP_001341797.1
TYMSOS	NR_171001.1	n.228C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYMS	ENST00000323274.15	c.205+117G>C		intron_variant	Intron 1 of 6	1	NM_001071.4	ENSP00000315644.10

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33786 AN: 152004 Hom.: 4879 Cov.: 33

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

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.: 32 AF XY: 0.168 AC XY: 118098 AN XY: 703284

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.: 33 AF XY: 0.225 AC XY: 16705 AN XY: 74358

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

Other links and lift over

dbSNP: rs2853533; hg19: chr18-658064; COSMIC: COSV60074757; COSMIC: COSV60074757;