chr18-675787-C-T

Position:

• chr18-675787-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.1149-385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,106 control chromosomes in the GnomAD database, including 44,530 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 0.76 (44530 hom., cov: 32)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1149-385G>A		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1149-385G>A		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115859 AN: 151988 Hom.: 44487 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.762 AC: 115956 AN: 152106 Hom.: 44530 Cov.: 32 AF XY: 0.758 AC XY: 56320 AN XY: 74336

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.762

Alfa AF: 0.751 Hom.: 41747

Bravo AF: 0.772

Asia WGS AF: 0.685 AC: 2386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.4
DANN	Benign	0.35

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: rs2260821; hg19: chr18-675787;