chr18-671520-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017512.7(ENOSF1):​c.*2785G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 988,694 control chromosomes in the GnomAD database, including 67,077 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 0.40 ( 13104 hom., cov: 32)
Exomes 𝑓: 0.35 ( 53973 hom. )

Consequence

ENOSF1
NM_017512.7 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

16 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]
TYMS (HGNC:12441): (thymidylate synthetase) Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]

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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 = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENOSF1NM_017512.7 linkc.*2785G>A 3_prime_UTR_variant Exon 16 of 16 ENST00000647584.2 NP_059982.2 Q7L5Y1-1
TYMSNM_001071.4 linkc.804+69C>T intron_variant Intron 6 of 6 ENST00000323274.15 NP_001062.1 P04818-1Q53Y97

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENOSF1ENST00000647584.2 linkc.*2785G>A 3_prime_UTR_variant Exon 16 of 16 NM_017512.7 ENSP00000497230.2 Q7L5Y1-1
TYMSENST00000323274.15 linkc.804+69C>T intron_variant Intron 6 of 6 1 NM_001071.4 ENSP00000315644.10 P04818-1

Frequencies

GnomAD3 genomes
AF:
0.398
AC:
60396
AN:
151888
Hom.:
13089
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.552
Gnomad AMI
AF:
0.166
Gnomad AMR
AF:
0.336
Gnomad ASJ
AF:
0.393
Gnomad EAS
AF:
0.686
Gnomad SAS
AF:
0.448
Gnomad FIN
AF:
0.304
Gnomad MID
AF:
0.478
Gnomad NFE
AF:
0.310
Gnomad OTH
AF:
0.399
GnomAD4 exome
AF:
0.346
AC:
289212
AN:
836688
Hom.:
53973
Cov.:
11
AF XY:
0.350
AC XY:
154451
AN XY:
441520
show subpopulations
African (AFR)
AF:
0.556
AC:
11708
AN:
21058
American (AMR)
AF:
0.324
AC:
13531
AN:
41782
Ashkenazi Jewish (ASJ)
AF:
0.381
AC:
8401
AN:
22070
East Asian (EAS)
AF:
0.666
AC:
24518
AN:
36808
South Asian (SAS)
AF:
0.439
AC:
31722
AN:
72212
European-Finnish (FIN)
AF:
0.301
AC:
15750
AN:
52248
Middle Eastern (MID)
AF:
0.482
AC:
2193
AN:
4554
European-Non Finnish (NFE)
AF:
0.305
AC:
166673
AN:
546128
Other (OTH)
AF:
0.369
AC:
14716
AN:
39828
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
9683
19367
29050
38734
48417
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3552
7104
10656
14208
17760
<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:
0.398
AC:
60443
AN:
152006
Hom.:
13104
Cov.:
32
AF XY:
0.402
AC XY:
29852
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.552
AC:
22871
AN:
41442
American (AMR)
AF:
0.335
AC:
5123
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.393
AC:
1365
AN:
3472
East Asian (EAS)
AF:
0.685
AC:
3548
AN:
5176
South Asian (SAS)
AF:
0.446
AC:
2146
AN:
4814
European-Finnish (FIN)
AF:
0.304
AC:
3209
AN:
10550
Middle Eastern (MID)
AF:
0.473
AC:
139
AN:
294
European-Non Finnish (NFE)
AF:
0.310
AC:
21044
AN:
67966
Other (OTH)
AF:
0.401
AC:
847
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1775
3551
5326
7102
8877
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
570
1140
1710
2280
2850
<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:
0.228
Hom.:
543
Bravo
AF:
0.407
Asia WGS
AF:
0.576
AC:
2005
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
0.75
DANN
Benign
0.53
PhyloP100
-1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2853536; hg19: chr18-671520; COSMIC: COSV51893080; COSMIC: COSV51893080; API