Variant 18-671520-C-T 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.*2785G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 988,694 control chromosomes in the GnomAD database, including 67,077 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 0.40 ( 13104 hom., cov: 32)

Exomes 𝑓: 0.35 ( 53973 hom. )

Consequence

ENOSF1
NM_017512.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7 link	c.*2785G>A		3_prime_UTR_variant	16/16	ENST00000647584.2	NP_059982.2	Q7L5Y1-1
TYMS	NM_001071.4 link	c.804+69C>T		intron_variant		ENST00000323274.15	NP_001062.1	P04818-1Q53Y97

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584 link	c.*2785G>A		3_prime_UTR_variant	16/16		NM_017512.7	ENSP00000497230.2		Q7L5Y1-1
TYMS	ENST00000323274.15 link	c.804+69C>T		intron_variant		1	NM_001071.4	ENSP00000315644.10		P04818-1

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60396

AN:

151888

Hom.:

13089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.686

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.399

GnomAD4 exome

AF:

0.346

AC:

289212

AN:

836688

Hom.:

53973

Cov.:

AF XY:

0.350

AC XY:

154451

AN XY:

441520

show subpopulations

Gnomad4 AFR exome

AF:

0.556

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.381

Gnomad4 EAS exome

AF:

0.666

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.398

AC:

60443

AN:

152006

Hom.:

13104

Cov.:

AF XY:

0.402

AC XY:

29852

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.552

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.685

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.208

Hom.:

429

Bravo

AF:

0.407

Asia WGS

AF:

0.576

AC:

2005

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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