rs3819102

chr18-675307-A-G

Variant summary

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

The NM_017512.7(ENOSF1):c.1230+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,603,502 control chromosomes in the GnomAD database, including 1,740 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 0.038 (253 hom., cov: 33)
  • Exomes 𝑓: 0.026 (1487 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1230+14T>C		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1230+14T>C		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5766 AN: 152188 Hom.: 251 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0448 AC: 10647 AN: 237900 Hom.: 721 AF XY: 0.0410 AC XY: 5246 AN XY: 127990

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.0427

Gnomad ASJ exome AF: 0.00711

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.0187

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0258 AC: 37474 AN: 1451196 Hom.: 1487 Cov.: 30 AF XY: 0.0250 AC XY: 18014 AN XY: 721020

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.00762

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.0190

Gnomad4 FIN exome AF: 0.0705

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0323

GnomAD4 genome AF: 0.0379 AC: 5779 AN: 152306 Hom.: 253 Cov.: 33 AF XY: 0.0410 AC XY: 3053 AN XY: 74470

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0261 Hom.: 110

Bravo AF: 0.0376

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.55
Dann	Benign	0.30

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: rs3819102; hg19: chr18-675307;