Variant 18-673086-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017512.7(ENOSF1):c.*1219T>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 0.218 in 1,377,150 control chromosomes in the GnomAD database, including 34,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4066 hom., cov: 32)

Exomes 𝑓: 0.22 ( 30107 hom. )

Consequence

ENOSF1
NM_017512.7 3_prime_UTR

Scores

Splicing: ADA: 0.00003376

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.707

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-673086-A-G is Benign according to our data. Variant chr18-673086-A-G is described in ClinVar as [Benign]. Clinvar id is 1234187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7 link	c.*1219T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2	Q7L5Y1-1
TYMS	NM_001071.4 link	c.*89A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000323274.15	NP_001062.1	P04818-1Q53Y97

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584 link	c.*1219T>C		3_prime_UTR_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2		Q7L5Y1-1
TYMS	ENST00000323274.15 link	c.*89A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001071.4	ENSP00000315644.10		P04818-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34419

AN:

152052

Hom.:

4065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.217

AC:

265510

AN:

1224980

Hom.:

30107

Cov.:

AF XY:

0.220

AC XY:

131461

AN XY:

596762

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.226

AC:

34437

AN:

152170

Hom.:

4066

Cov.:

AF XY:

0.229

AC XY:

17064

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.216

Hom.:

3717

Bravo

AF:

0.231

Asia WGS

AF:

0.383

AC:

1336

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24997136) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over