dbSNP rs2298581: ENOSF1:c.919-59G>C (chr18-677931-C-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.919-59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,568,132 control chromosomes in the GnomAD database, including 39,152 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 0.22 ( 3986 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35166 hom. )

Consequence

ENOSF1
NM_017512.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

13 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 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.919-59G>C	intron	N/A	NP_059982.2
ENOSF1	NM_001354067.2		c.1063-59G>C	intron	N/A	NP_001340996.1
ENOSF1	NM_202758.5		c.1021-59G>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.919-59G>C	intron	N/A	ENSP00000497230.2	Q7L5Y1-1
ENOSF1	ENST00000383578.7	TSL:1	c.673-59G>C	intron	N/A	ENSP00000373072.3	Q7L5Y1-2
ENOSF1	ENST00000581475.5	TSL:1	n.*306-59G>C	intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34071

AN:

152020

Hom.:

3985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.218

AC:

308020

AN:

1415992

Hom.:

35166

Cov.:

AF XY:

0.222

AC XY:

155925

AN XY:

702078

show subpopulations

African (AFR)

AF:

0.258

AC:

8255

AN:

32032

American (AMR)

AF:

0.224

AC:

8796

AN:

39308

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

5907

AN:

24146

East Asian (EAS)

AF:

0.389

AC:

15102

AN:

38788

South Asian (SAS)

AF:

0.336

AC:

27051

AN:

80498

European-Finnish (FIN)

AF:

0.166

AC:

7492

AN:

45164

Middle Eastern (MID)

AF:

0.338

AC:

1883

AN:

5576

European-Non Finnish (NFE)

AF:

0.201

AC:

219826

AN:

1091912

Other (OTH)

AF:

0.234

AC:

13708

AN:

58568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11734

23468

35203

46937

58671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8052

16104

24156

32208

40260

<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:

0.224

AC:

34088

AN:

152140

Hom.:

3986

Cov.:

AF XY:

0.227

AC XY:

16854

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.248

AC:

10293

AN:

41512

American (AMR)

AF:

0.212

AC:

3236

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

897

AN:

3472

East Asian (EAS)

AF:

0.369

AC:

1906

AN:

5168

South Asian (SAS)

AF:

0.332

AC:

1599

AN:

4816

European-Finnish (FIN)

AF:

0.164

AC:

1736

AN:

10586

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13776

AN:

67994

Other (OTH)

AF:

0.243

AC:

512

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1365

2731

4096

5462

6827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.213

Hom.:

418

Bravo

AF:

0.229

Asia WGS

AF:

0.371

AC:

1294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

(source)

DANN

Benign

0.48

PhyloP100

-1.2

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

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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