rs2847154

Positions:

• chr18-687270-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.654-1262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,134 control chromosomes in the GnomAD database, including 3,393 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 0.20 (3392 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.654-1262C>T		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.654-1262C>T		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30675 AN: 152004 Hom.: 3388 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.500 AC: 6 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.202 AC: 30702 AN: 152122 Hom.: 3392 Cov.: 33 AF XY: 0.201 AC XY: 14922 AN XY: 74362

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00638

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.179

Alfa AF: 0.227 Hom.: 4922

Bravo AF: 0.200

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.066
DANN	Benign	0.63

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: rs2847154; hg19: chr18-687270;