18-675000-C-T

Position:

• chr18-675000-C-T

Variant summary

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

The NM_017512.7(ENOSF1):​c.1230+321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,038 control chromosomes in the GnomAD database, including 13,087 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 (13087 hom., cov: 33)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1230+321G>A		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1230+321G>A		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60563 AN: 151920 Hom.: 13074 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.404

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.399 AC: 60607 AN: 152038 Hom.: 13087 Cov.: 33 AF XY: 0.401 AC XY: 29815 AN XY: 74314

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.406

Alfa AF: 0.330 Hom.: 11074

Bravo AF: 0.407

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.23

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: rs9948583; hg19: chr18-675000;