chr18-674440-A-C

Position:

• chr18-674440-A-C

Variant summary

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

The NM_017512.7(ENOSF1):​c.1231-34T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,370,686 control chromosomes in the GnomAD database, including 83,142 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 0.36 (10184 hom., cov: 32)
  • Exomes 𝑓: 0.34 (72958 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.1231-34T>G		intron_variant		ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1231-34T>G		intron_variant			NM_017512.7	ENSP00000497230	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54141 AN: 151902 Hom.: 10177 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.369

GnomAD3 exomes AF: 0.373 AC: 84878 AN: 227544 Hom.: 17036 AF XY: 0.375 AC XY: 46358 AN XY: 123528

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.696

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.339 AC: 413541 AN: 1218666 Hom.: 72958 Cov.: 16 AF XY: 0.343 AC XY: 211847 AN XY: 617474

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.356 AC: 54168 AN: 152020 Hom.: 10184 Cov.: 32 AF XY: 0.361 AC XY: 26856 AN XY: 74302

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.372

Alfa AF: 0.339 Hom.: 16593

Bravo AF: 0.360

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs11081251; hg19: chr18-674440;