NM_017512.7:c.742-227G>A

Variant names:

• chr18-683607-C-T
• rs2612091
• NM_017512.7:c.742-227G>A

Variant summary

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

The NM_017512.7(ENOSF1):​c.742-227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,838 control chromosomes in the GnomAD database, including 30,343 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 0.62 (30343 hom., cov: 30)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 35 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017512.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	NM_017512.7	MANE Select	c.742-227G>A		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.886-227G>A		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.886-227G>A		intron	N/A	NP_974487.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.742-227G>A		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.496-227G>A		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*129-227G>A		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94658 AN: 151720 Hom.: 30303 Cov.: 30

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.624 AC: 94748 AN: 151838 Hom.: 30343 Cov.: 30 AF XY: 0.623 AC XY: 46195 AN XY: 74172

African (AFR) AF: 0.790 AC: 32743 AN: 41426

American (AMR) AF: 0.599 AC: 9137 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3526 AN: 5118

South Asian (SAS) AF: 0.512 AC: 2464 AN: 4808

European-Finnish (FIN) AF: 0.557 AC: 5861 AN: 10518

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37383 AN: 67924

Other (OTH) AF: 0.603 AC: 1273 AN: 2110

Alfa AF: 0.576 Hom.: 112943

Bravo AF: 0.636

Asia WGS AF: 0.626 AC: 2182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.40
PhyloP100		-1.1
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: rs2612091; hg19: chr18-683607;