rs2847326

Positions:

• chr18-676228-T-A

Variant summary

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

The NM_017512.7(ENOSF1):​c.1149-826A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,128 control chromosomes in the GnomAD database, including 4,805 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 0.24 (4805 hom., cov: 32)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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 (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.1149-826A>T		intron_variant		ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1149-826A>T		intron_variant			NM_017512.7	ENSP00000497230	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36822 AN: 152010 Hom.: 4797 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.242 AC: 36866 AN: 152128 Hom.: 4805 Cov.: 32 AF XY: 0.239 AC XY: 17742 AN XY: 74370

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.215

Alfa AF: 0.253 Hom.: 621

Bravo AF: 0.247

Asia WGS AF: 0.0620 AC: 219 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	10
DANN	Benign	0.82

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: rs2847326; hg19: chr18-676228;