Genetic Variant ENOSF1:c.1230+14T>C (chr18-675307-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017512.7(ENOSF1):c.1230+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,603,502 control chromosomes in the GnomAD database, including 1,740 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 0.038 ( 253 hom., cov: 33)

Exomes 𝑓: 0.026 ( 1487 hom. )

Consequence

ENOSF1
NM_017512.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.217

Publications

12 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017512.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENOSF1	NM_017512.7	MANE Select	c.1230+14T>C	intron	N/A	NP_059982.2
ENOSF1	NM_001354067.2		c.1374+14T>C	intron	N/A	NP_001340996.1
ENOSF1	NM_202758.5		c.1332+14T>C	intron	N/A	NP_974487.2	A0A3F2YNX7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENOSF1	ENST00000647584.2	MANE Select	c.1230+14T>C	intron	N/A	ENSP00000497230.2	Q7L5Y1-1
ENOSF1	ENST00000383578.7	TSL:1	c.984+14T>C	intron	N/A	ENSP00000373072.3	Q7L5Y1-2
ENOSF1	ENST00000581475.5	TSL:1	n.*617+14T>C	intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5766

AN:

152188

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0448

AC:

10647

AN:

237900

AF XY:

0.0410

show subpopulations

Gnomad AFR exome

AF:

0.0478

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.00711

Gnomad EAS exome

AF:

0.262

Gnomad FIN exome

AF:

0.0732

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0328

GnomAD4 exome

AF:

0.0258

AC:

37474

AN:

1451196

Hom.:

1487

Cov.:

AF XY:

0.0250

AC XY:

18014

AN XY:

721020

show subpopulations

African (AFR)

AF:

0.0458

AC:

1528

AN:

33354

American (AMR)

AF:

0.0405

AC:

1756

AN:

43394

Ashkenazi Jewish (ASJ)

AF:

0.00762

AC:

197

AN:

25856

East Asian (EAS)

AF:

0.224

AC:

8828

AN:

39484

South Asian (SAS)

AF:

0.0190

AC:

1596

AN:

84024

European-Finnish (FIN)

AF:

0.0705

AC:

3718

AN:

52734

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5350

European-Non Finnish (NFE)

AF:

0.0161

AC:

17847

AN:

1106966

Other (OTH)

AF:

0.0323

AC:

1941

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1702

3403

5105

6806

8508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

840

1680

2520

3360

4200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0379

AC:

5779

AN:

152306

Hom.:

253

Cov.:

AF XY:

0.0410

AC XY:

3053

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0503

AC:

2091

AN:

41582

American (AMR)

AF:

0.0246

AC:

376

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1271

AN:

5174

South Asian (SAS)

AF:

0.0242

AC:

117

AN:

4834

European-Finnish (FIN)

AF:

0.0744

AC:

789

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0151

AC:

1027

AN:

68024

Other (OTH)

AF:

0.0331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

270

541

811

1082

1352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0264

Hom.:

399

Bravo

AF:

0.0376

Asia WGS

AF:

0.121

AC:

420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

(source)

DANN

Benign

0.30

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over