rs1059384

Variant names:

• chr18-673995-T-C
• rs1059384
• NM_017512.7:c.*310A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-673995-T-C
• chr18-673995-T-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.*310A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 207,324 control chromosomes in the GnomAD database, including 16,879 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 (13098 hom., cov: 31)
  • Exomes 𝑓: 0.35 (3781 hom.)
• Consequence: ENOSF1 NM_017512.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 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.*310A>G		3_prime_UTR	Exon 16 of 16	NP_059982.2
	ENOSF1	NM_001354067.2		c.*310A>G		3_prime_UTR	Exon 16 of 16	NP_001340996.1
	ENOSF1	NM_202758.5		c.*310A>G		3_prime_UTR	Exon 15 of 15	NP_974487.2	A0A3F2YNX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.*310A>G		3_prime_UTR	Exon 16 of 16	ENSP00000497230.2	Q7L5Y1-1
	ENOSF1	ENST00000383578.7	TSL:1	c.*144+166A>G		intron	N/A	ENSP00000373072.3	Q7L5Y1-2
	ENOSF1	ENST00000581475.5	TSL:1	n.*1029A>G		non_coding_transcript_exon	Exon 14 of 14	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60312 AN: 151736 Hom.: 13083 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.354 AC: 19621 AN: 55470 Hom.: 3781 Cov.: 0 AF XY: 0.357 AC XY: 10115 AN XY: 28314

African (AFR) AF: 0.567 AC: 986 AN: 1738

American (AMR) AF: 0.326 AC: 648 AN: 1986

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 778 AN: 1976

East Asian (EAS) AF: 0.702 AC: 2110 AN: 3004

South Asian (SAS) AF: 0.425 AC: 1434 AN: 3378

European-Finnish (FIN) AF: 0.309 AC: 822 AN: 2664

Middle Eastern (MID) AF: 0.448 AC: 120 AN: 268

European-Non Finnish (NFE) AF: 0.309 AC: 11336 AN: 36682

Other (OTH) AF: 0.368 AC: 1387 AN: 3774

GnomAD4 genome AF: 0.397 AC: 60359 AN: 151854 Hom.: 13098 Cov.: 31 AF XY: 0.401 AC XY: 29789 AN XY: 74214

African (AFR) AF: 0.552 AC: 22830 AN: 41368

American (AMR) AF: 0.335 AC: 5111 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3538 AN: 5166

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4808

European-Finnish (FIN) AF: 0.303 AC: 3195 AN: 10540

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21024 AN: 67948

Other (OTH) AF: 0.400 AC: 843 AN: 2108

Alfa AF: 0.328 Hom.: 9542

Bravo AF: 0.407

Asia WGS AF: 0.575 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		0.13
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: rs1059384; hg19: chr18-673995;