18-682399-C-T

Position:

• chr18-682399-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.876+847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 152,240 control chromosomes in the GnomAD database, including 537 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 0.072 (537 hom., cov: 31)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392

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]

ENOSF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.876+847G>A		intron_variant		ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.876+847G>A		intron_variant			NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10955 AN: 152122 Hom.: 537 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0720 AC: 10954 AN: 152240 Hom.: 537 Cov.: 31 AF XY: 0.0710 AC XY: 5282 AN XY: 74444

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0951 Hom.: 1302

Bravo AF: 0.0626

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.67

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: rs2612092; hg19: chr18-682399;