18-677452-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017512.7(ENOSF1):c.1049-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,610,548 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (39 hom.)
• Consequence: ENOSF1 NM_017512.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008796
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.220

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-677452-G-A is Benign according to our data. Variant chr18-677452-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1049-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1049-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.00422 AC: 643 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00444 AC: 1098 AN: 247046 Hom.: 5 AF XY: 0.00449 AC XY: 600 AN XY: 133702

Gnomad AFR exome AF: 0.000682

Gnomad AMR exome AF: 0.00308

Gnomad ASJ exome AF: 0.00141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00508

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00666

Gnomad OTH exome AF: 0.00531

GnomAD4 exome AF: 0.00624 AC: 9103 AN: 1458236 Hom.: 39 Cov.: 30 AF XY: 0.00617 AC XY: 4475 AN XY: 725530

Gnomad4 AFR exome AF: 0.000934

Gnomad4 AMR exome AF: 0.00317

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00462

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00720

Gnomad4 OTH exome AF: 0.00599

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.00362 AC XY: 270 AN XY: 74488

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00651

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00478 Hom.: 2

Bravo AF: 0.00459

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ENOSF1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.1
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000088
dbscSNV1_RF	Benign	0.0040
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: rs190795784; hg19: chr18-677452; COSMIC: COSV51893068; COSMIC: COSV51893068;