Variant chr18-658147-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001071.4(TYMS):c.205+200C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,583,902 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 4 hom., cov: 33)

Exomes 𝑓: 0.010 ( 88 hom. )

Consequence

TYMS
NM_001071.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.722

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 18-658147-C-A is Benign according to our data. Variant chr18-658147-C-A is described in ClinVar as [Benign]. Clinvar id is 2648512.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TYMS	NM_001071.4 linkuse as main transcript	c.205+200C>A	intron_variant		ENST00000323274.15
TYMSOS	NR_171001.1 linkuse as main transcript	n.145G>T	non_coding_transcript_exon_variant	1/2
TYMS	NM_001354867.2 linkuse as main transcript	c.205+200C>A	intron_variant
TYMS	NM_001354868.2 linkuse as main transcript	c.205+200C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYMS	ENST00000323274.15 linkuse as main transcript	c.205+200C>A		intron_variant		1	NM_001071.4	P1	P04818-1
TYMSOS	ENST00000585033.1 linkuse as main transcript	n.123G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00787

AC:

1196

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00751

AC:

1546

AN:

205736

Hom.:

AF XY:

0.00748

AC XY:

851

AN XY:

113728

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00787

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00253

Gnomad FIN exome

AF:

0.00161

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0102

AC:

14546

AN:

1431848

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7126

AN XY:

711104

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.00810

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00241

Gnomad4 FIN exome

AF:

0.00249

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.00983

GnomAD4 genome

AF:

0.00786

AC:

1195

AN:

152054

Hom.:

Cov.:

AF XY:

0.00749

AC XY:

557

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00818

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

TYMSOS: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.7

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over