rs10502289

Variant names:

• chr18-676789-A-T
• rs10502289
• NM_017512.7:c.1148+556T>A

Variant summary

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

The NM_017512.7(ENOSF1):​c.1148+556T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,134 control chromosomes in the GnomAD database, including 2,167 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 0.15 (2167 hom., cov: 33)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 16 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 (SAS) allele frequency at 95% confidence interval = 0.238 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.1148+556T>A		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1292+556T>A		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1250+556T>A		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.1148+556T>A		intron	N/A	ENSP00000497230.2	Q7L5Y1-1
	ENOSF1	ENST00000383578.7	TSL:1	c.902+556T>A		intron	N/A	ENSP00000373072.3	Q7L5Y1-2
	ENOSF1	ENST00000581475.5	TSL:1	n.*535+556T>A		intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22926 AN: 152016 Hom.: 2168 Cov.: 33

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152134 Hom.: 2167 Cov.: 33 AF XY: 0.152 AC XY: 11314 AN XY: 74364

African (AFR) AF: 0.0370 AC: 1537 AN: 41524

American (AMR) AF: 0.162 AC: 2473 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.182 AC: 938 AN: 5166

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1729 AN: 10578

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13653 AN: 67984

Other (OTH) AF: 0.184 AC: 388 AN: 2108

Alfa AF: 0.199 Hom.: 1705

Bravo AF: 0.144

Asia WGS AF: 0.223 AC: 777 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	0.23
DANN	Benign	0.45
PhyloP100		-1.8
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: rs10502289; hg19: chr18-676789;