rs2298583

Positions:

• chr18-677302-G-A

Variant summary

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

The NM_017512.7(ENOSF1):​c.1148+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,515,520 control chromosomes in the GnomAD database, including 82,263 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 0.34 (9274 hom., cov: 32)
  • Exomes 𝑓: 0.32 (72989 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1148+43C>T		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1148+43C>T		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52131 AN: 151876 Hom.: 9267 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.337 AC: 83169 AN: 246806 Hom.: 14439 AF XY: 0.343 AC XY: 45747 AN XY: 133482

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.422

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.322 AC: 439400 AN: 1363526 Hom.: 72989 Cov.: 19 AF XY: 0.327 AC XY: 223402 AN XY: 683932

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.343 AC: 52162 AN: 151994 Hom.: 9274 Cov.: 32 AF XY: 0.343 AC XY: 25487 AN XY: 74290

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.362

Alfa AF: 0.326 Hom.: 3777

Bravo AF: 0.349

Asia WGS AF: 0.471 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2298583; hg19: chr18-677302; COSMIC: COSV51896328; COSMIC: COSV51896328;