Variant rs1059393 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017512.7(ENOSF1):c.*1469T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,544,122 control chromosomes in the GnomAD database, including 16,105 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 0.13 ( 1295 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14810 hom. )

Consequence

ENOSF1
NM_017512.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

ENOSF1 (HGNC:30365): (enolase superfamily member 1) This gene can encode a mitochondrial enzyme that is thought to convert L-fuconate to 2-keto-3-deoxy-L-fuconate. This locus was originally identified as the source of antisense RNAs of the adjacent thymidylate synthase gene. Splice variants at this locus may contain an alternate 3' exon that is complementary to the 3'UTR and terminal intron of the thymidylate synthase (TS) RNA and may downregulate TS expression. [provided by RefSeq, Aug 2017]

ENOSF1 links:

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:

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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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7 linkuse as main transcript	c.*1469T>C		3_prime_UTR_variant	16/16	ENST00000647584.2
TYMS	NM_001071.4 linkuse as main transcript	c.805-24A>G		intron_variant		ENST00000323274.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2 linkuse as main transcript	c.*1469T>C		3_prime_UTR_variant	16/16		NM_017512.7	P1	Q7L5Y1-1
TYMS	ENST00000323274.15 linkuse as main transcript	c.805-24A>G		intron_variant		1	NM_001071.4	P1	P04818-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19121

AN:

152118

Hom.:

1291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.0853

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.117

AC:

28773

AN:

246432

Hom.:

1965

AF XY:

0.119

AC XY:

15857

AN XY:

133708

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.0633

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.00418

Gnomad SAS exome

AF:

0.0974

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.141

AC:

196084

AN:

1391886

Hom.:

14810

Cov.:

AF XY:

0.139

AC XY:

95171

AN XY:

684788

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0676

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.00297

Gnomad4 SAS exome

AF:

0.0947

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.126

AC:

19138

AN:

152236

Hom.:

1295

Cov.:

AF XY:

0.122

AC XY:

9118

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0850

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0860

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.139

Hom.:

1404

Bravo

AF:

0.121

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.4

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over