rs2298582

chr18-677621-T-G

Variant summary

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

The NM_017512.7(ENOSF1):c.1048+122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,375,018 control chromosomes in the GnomAD database, including 7,142 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 0.091 (718 hom., cov: 33)
  • Exomes 𝑓: 0.10 (6424 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.1048+122A>C		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1048+122A>C		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13857 AN: 151690 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0997 AC: 121948 AN: 1223210 Hom.: 6424 Cov.: 17 AF XY: 0.0998 AC XY: 60457 AN XY: 605826

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.0609

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0741

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.0698

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0913 AC: 13857 AN: 151808 Hom.: 718 Cov.: 33 AF XY: 0.0903 AC XY: 6703 AN XY: 74228

Gnomad4 AFR AF: 0.0683

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.101

Alfa AF: 0.106 Hom.: 1264

Bravo AF: 0.0893

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.7
Dann	Benign	0.42

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: rs2298582; hg19: chr18-677621;