rs2298581

Variant names:

• chr18-677931-C-G
• rs2298581
• NM_017512.7:c.919-59G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017512.7(ENOSF1):​c.919-59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,568,132 control chromosomes in the GnomAD database, including 39,152 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 (3986 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35166 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.919-59G>C		intron_variant	Intron 12 of 15	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.919-59G>C		intron_variant	Intron 12 of 15		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34071 AN: 152020 Hom.: 3985 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.218 AC: 308020 AN: 1415992 Hom.: 35166 Cov.: 27 AF XY: 0.222 AC XY: 155925 AN XY: 702078

African (AFR) AF: 0.258 AC: 8255 AN: 32032

American (AMR) AF: 0.224 AC: 8796 AN: 39308

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 5907 AN: 24146

East Asian (EAS) AF: 0.389 AC: 15102 AN: 38788

South Asian (SAS) AF: 0.336 AC: 27051 AN: 80498

European-Finnish (FIN) AF: 0.166 AC: 7492 AN: 45164

Middle Eastern (MID) AF: 0.338 AC: 1883 AN: 5576

European-Non Finnish (NFE) AF: 0.201 AC: 219826 AN: 1091912

Other (OTH) AF: 0.234 AC: 13708 AN: 58568

GnomAD4 genome AF: 0.224 AC: 34088 AN: 152140 Hom.: 3986 Cov.: 33 AF XY: 0.227 AC XY: 16854 AN XY: 74364

African (AFR) AF: 0.248 AC: 10293 AN: 41512

American (AMR) AF: 0.212 AC: 3236 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 897 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5168

South Asian (SAS) AF: 0.332 AC: 1599 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1736 AN: 10586

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13776 AN: 67994

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.213 Hom.: 418

Bravo AF: 0.229

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298581; hg19: chr18-677931;