chr18-681724-C-T

Position:

• chr18-681724-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+1522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,106 control chromosomes in the GnomAD database, including 3,795 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 0.22 (3795 hom., cov: 32)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.867

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.876+1522G>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+1522G>A		intron_variant			NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32834 AN: 151988 Hom.: 3790 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.216 AC: 32869 AN: 152106 Hom.: 3795 Cov.: 32 AF XY: 0.214 AC XY: 15891 AN XY: 74370

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.00349

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.197

Alfa AF: 0.166 Hom.: 463

Bravo AF: 0.217

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2847607; hg19: chr18-681724;