Genetic Variant NM_017512.7:c.1048+122A>C (chr18-677621-T-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.1048+122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,375,018 control chromosomes in the GnomAD database, including 7,142 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 0.091 ( 718 hom., cov: 33)

Exomes 𝑓: 0.10 ( 6424 hom. )

Consequence

ENOSF1
NM_017512.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920

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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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
ENOSF1	NM_017512.7	MANE Select	c.1048+122A>C	intron	N/A	NP_059982.2
ENOSF1	NM_001354067.2		c.1192+122A>C	intron	N/A	NP_001340996.1
ENOSF1	NM_202758.5		c.1150+122A>C	intron	N/A	NP_974487.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENOSF1	ENST00000647584.2	MANE Select	c.1048+122A>C	intron	N/A	ENSP00000497230.2
ENOSF1	ENST00000383578.7	TSL:1	c.802+122A>C	intron	N/A	ENSP00000373072.3
ENOSF1	ENST00000581475.5	TSL:1	n.*435+122A>C	intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

13857

AN:

151690

Hom.:

718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0684

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0790

Gnomad SAS

AF:

0.0894

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0997

AC:

121948

AN:

1223210

Hom.:

6424

Cov.:

AF XY:

0.0998

AC XY:

60457

AN XY:

605826

show subpopulations

African (AFR)

AF:

0.0671

AC:

1829

AN:

27252

American (AMR)

AF:

0.0609

AC:

1669

AN:

27406

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

2556

AN:

19206

East Asian (EAS)

AF:

0.0741

AC:

2789

AN:

37652

South Asian (SAS)

AF:

0.0806

AC:

5237

AN:

64960

European-Finnish (FIN)

AF:

0.0698

AC:

2997

AN:

42934

Middle Eastern (MID)

AF:

0.117

AC:

408

AN:

3478

European-Non Finnish (NFE)

AF:

0.105

AC:

99289

AN:

948710

Other (OTH)

AF:

0.100

AC:

5174

AN:

51612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5379

10759

16138

21518

26897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3500

7000

10500

14000

17500

<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:

0.0913

AC:

13857

AN:

151808

Hom.:

718

Cov.:

AF XY:

0.0903

AC XY:

6703

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.0683

AC:

2823

AN:

41304

American (AMR)

AF:

0.0825

AC:

1259

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3468

East Asian (EAS)

AF:

0.0794

AC:

409

AN:

5152

South Asian (SAS)

AF:

0.0892

AC:

428

AN:

4796

European-Finnish (FIN)

AF:

0.0744

AC:

786

AN:

10562

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7334

AN:

67942

Other (OTH)

AF:

0.101

AC:

213

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

659

1318

1978

2637

3296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.103

Hom.:

2516

Bravo

AF:

0.0893

Asia WGS

AF:

0.0950

AC:

329

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.42

PhyloP100

-0.092

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