Genetic Variant NM_017512.7:c.1231-34T>G (chr18-674440-A-C) – 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.1231-34T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,370,686 control chromosomes in the GnomAD database, including 83,142 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 0.36 ( 10184 hom., cov: 32)

Exomes 𝑓: 0.34 ( 72958 hom. )

Consequence

ENOSF1
NM_017512.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

Publications

15 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7 link	c.1231-34T>G		intron_variant	Intron 15 of 15	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2 link	c.1231-34T>G		intron_variant	Intron 15 of 15		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54141

AN:

151902

Hom.:

10177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.373

AC:

84878

AN:

227544

AF XY:

0.375

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.339

AC:

413541

AN:

1218666

Hom.:

72958

Cov.:

AF XY:

0.343

AC XY:

211847

AN XY:

617474

show subpopulations

African (AFR)

AF:

0.427

AC:

11785

AN:

27570

American (AMR)

AF:

0.321

AC:

12233

AN:

38114

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

9234

AN:

23724

East Asian (EAS)

AF:

0.669

AC:

25505

AN:

38134

South Asian (SAS)

AF:

0.443

AC:

34183

AN:

77224

European-Finnish (FIN)

AF:

0.302

AC:

15915

AN:

52744

Middle Eastern (MID)

AF:

0.483

AC:

2504

AN:

5188

European-Non Finnish (NFE)

AF:

0.313

AC:

283179

AN:

903896

Other (OTH)

AF:

0.365

AC:

19003

AN:

52072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

13305

26609

39914

53218

66523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8878

17756

26634

35512

44390

<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:

0.356

AC:

54168

AN:

152020

Hom.:

10184

Cov.:

AF XY:

0.361

AC XY:

26856

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.408

AC:

16914

AN:

41446

American (AMR)

AF:

0.322

AC:

4914

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1376

AN:

3470

East Asian (EAS)

AF:

0.685

AC:

3536

AN:

5164

South Asian (SAS)

AF:

0.446

AC:

2144

AN:

4808

European-Finnish (FIN)

AF:

0.304

AC:

3214

AN:

10562

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

20998

AN:

67978

Other (OTH)

AF:

0.372

AC:

782

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1758

3517

5275

7034

8792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.340

Hom.:

23511

Bravo

AF:

0.360

Asia WGS

AF:

0.569

AC:

1979

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

(source)

DANN

Benign

0.27

PhyloP100

-0.039

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over