Genetic Variant NM_017512.7:c.1148+43C>T (chr18-677302-G-A) – 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.1148+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,515,520 control chromosomes in the GnomAD database, including 82,263 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 0.34 ( 9274 hom., cov: 32)

Exomes 𝑓: 0.32 ( 72989 hom. )

Consequence

ENOSF1
NM_017512.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0450

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 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.1148+43C>T	intron	N/A	NP_059982.2
ENOSF1	NM_001354067.2		c.1292+43C>T	intron	N/A	NP_001340996.1
ENOSF1	NM_202758.5		c.1250+43C>T	intron	N/A	NP_974487.2	A0A3F2YNX7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENOSF1	ENST00000647584.2	MANE Select	c.1148+43C>T	intron	N/A	ENSP00000497230.2	Q7L5Y1-1
ENOSF1	ENST00000383578.7	TSL:1	c.902+43C>T	intron	N/A	ENSP00000373072.3	Q7L5Y1-2
ENOSF1	ENST00000581475.5	TSL:1	n.*535+43C>T	intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52131

AN:

151876

Hom.:

9267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.337

AC:

83169

AN:

246806

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.322

AC:

439400

AN:

1363526

Hom.:

72989

Cov.:

AF XY:

0.327

AC XY:

223402

AN XY:

683932

show subpopulations

African (AFR)

AF:

0.429

AC:

13454

AN:

31364

American (AMR)

AF:

0.285

AC:

12407

AN:

43508

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9577

AN:

25438

East Asian (EAS)

AF:

0.465

AC:

18185

AN:

39148

South Asian (SAS)

AF:

0.418

AC:

34924

AN:

83490

European-Finnish (FIN)

AF:

0.237

AC:

12618

AN:

53160

Middle Eastern (MID)

AF:

0.457

AC:

2553

AN:

5586

European-Non Finnish (NFE)

AF:

0.309

AC:

316198

AN:

1024910

Other (OTH)

AF:

0.342

AC:

19484

AN:

56922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14411

28822

43234

57645

72056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10236

20472

30708

40944

51180

<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:

0.343

AC:

52162

AN:

151994

Hom.:

9274

Cov.:

AF XY:

0.343

AC XY:

25487

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.413

AC:

17128

AN:

41440

American (AMR)

AF:

0.305

AC:

4652

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3470

East Asian (EAS)

AF:

0.448

AC:

2309

AN:

5154

South Asian (SAS)

AF:

0.423

AC:

2033

AN:

4810

European-Finnish (FIN)

AF:

0.238

AC:

2516

AN:

10566

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21124

AN:

67976

Other (OTH)

AF:

0.362

AC:

766

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1777

3555

5332

7110

8887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.328

Hom.:

4455

Bravo

AF:

0.349

Asia WGS

AF:

0.471

AC:

1642

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.3

(source)

DANN

Benign

0.34

PhyloP100

0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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