rs2298581

chr18-677931-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017512.7(ENOSF1):c.919-59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,568,132 control chromosomes in the GnomAD database, including 39,152 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 0.22 (3986 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35166 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.919-59G>C		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.919-59G>C		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34071 AN: 152020 Hom.: 3985 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.218 AC: 308020 AN: 1415992 Hom.: 35166 Cov.: 27 AF XY: 0.222 AC XY: 155925 AN XY: 702078

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.224 AC: 34088 AN: 152140 Hom.: 3986 Cov.: 33 AF XY: 0.227 AC XY: 16854 AN XY: 74364

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.243

Alfa AF: 0.213 Hom.: 418

Bravo AF: 0.229

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.8
Dann	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs2298581; hg19: chr18-677931;