18-676008-G-C

Variant names:

• chr18-676008-G-C
• rs495139
• NM_017512.7:c.1149-606C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017512.7(ENOSF1):​c.1149-606C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,938 control chromosomes in the GnomAD database, including 29,822 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 0.63 (29822 hom., cov: 31)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	NM_017512.7	MANE Select	c.1149-606C>G		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1293-606C>G		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1251-606C>G		intron	N/A	NP_974487.2	A0A3F2YNX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.1149-606C>G		intron	N/A	ENSP00000497230.2	Q7L5Y1-1
	ENOSF1	ENST00000383578.7	TSL:1	c.903-606C>G		intron	N/A	ENSP00000373072.3	Q7L5Y1-2
	ENOSF1	ENST00000581475.5	TSL:1	n.*536-606C>G		intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94918 AN: 151820 Hom.: 29795 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 94993 AN: 151938 Hom.: 29822 Cov.: 31 AF XY: 0.625 AC XY: 46406 AN XY: 74246

African (AFR) AF: 0.711 AC: 29440 AN: 41426

American (AMR) AF: 0.615 AC: 9388 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1876 AN: 3460

East Asian (EAS) AF: 0.690 AC: 3557 AN: 5158

South Asian (SAS) AF: 0.547 AC: 2634 AN: 4814

European-Finnish (FIN) AF: 0.596 AC: 6297 AN: 10560

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39819 AN: 67948

Other (OTH) AF: 0.622 AC: 1311 AN: 2108

Alfa AF: 0.604 Hom.: 3461

Bravo AF: 0.632

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-2.4
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

Other links and lift over

dbSNP: rs495139; hg19: chr18-676008;