18-674440-A-C

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
ENOSF1NM_017512.7 linkuse as main transcriptc.1231-34T>G intron_variant ENST00000647584.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ENOSF1ENST00000647584.2 linkuse as main transcriptc.1231-34T>G intron_variant NM_017512.7 P1Q7L5Y1-1

Frequencies

GnomAD3 genomes
AF:
0.356
AC:
54141
AN:
151902
Hom.:
10177
Cov.:
32
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
GnomAD3 exomes
AF:
0.373
AC:
84878
AN:
227544
Hom.:
17036
AF XY:
0.375
AC XY:
46358
AN XY:
123528
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 SAS exome
AF:
0.450
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.:
16
AF XY:
0.343
AC XY:
211847
AN XY:
617474
show subpopulations
Gnomad4 AFR exome
AF:
0.427
Gnomad4 AMR exome
AF:
0.321
Gnomad4 ASJ exome
AF:
0.389
Gnomad4 EAS exome
AF:
0.669
Gnomad4 SAS exome
AF:
0.443
Gnomad4 FIN exome
AF:
0.302
Gnomad4 NFE exome
AF:
0.313
Gnomad4 OTH exome
AF:
0.365
GnomAD4 genome
AF:
0.356
AC:
54168
AN:
152020
Hom.:
10184
Cov.:
32
AF XY:
0.361
AC XY:
26856
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.408
Gnomad4 AMR
AF:
0.322
Gnomad4 ASJ
AF:
0.397
Gnomad4 EAS
AF:
0.685
Gnomad4 SAS
AF:
0.446
Gnomad4 FIN
AF:
0.304
Gnomad4 NFE
AF:
0.309
Gnomad4 OTH
AF:
0.372
Alfa
AF:
0.339
Hom.:
16593
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
13
DANN
Benign
0.27
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11081251; hg19: chr18-674440; API