18-700687-T-C

Variant names:

• chr18-700687-T-C
• rs2741171
• NM_017512.7:c.194-3332A>G

Variant summary

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

The NM_017512.7(ENOSF1):​c.194-3332A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,492 control chromosomes in the GnomAD database, including 30,615 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 0.63 (30615 hom., cov: 29)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91
• Publications: 10 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=-0.95).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	NM_017512.7	MANE Select	c.194-3332A>G		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.338-3332A>G		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.338-3332A>G		intron	N/A	NP_974487.2	A0A3F2YNX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOSF1	ENST00000647584.2	MANE Select	c.194-3332A>G		intron	N/A	ENSP00000497230.2	Q7L5Y1-1
	ENOSF1	ENST00000383578.7	TSL:1	c.63+5783A>G		intron	N/A	ENSP00000373072.3	Q7L5Y1-2
	ENOSF1	ENST00000581475.5	TSL:1	n.194-3332A>G		intron	N/A	ENSP00000464614.1	J3QSB6

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95166 AN: 151376 Hom.: 30562 Cov.: 29

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.629 AC: 95272 AN: 151492 Hom.: 30615 Cov.: 29 AF XY: 0.627 AC XY: 46372 AN XY: 73986

African (AFR) AF: 0.791 AC: 32657 AN: 41308

American (AMR) AF: 0.603 AC: 9185 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1769 AN: 3456

East Asian (EAS) AF: 0.680 AC: 3485 AN: 5122

South Asian (SAS) AF: 0.548 AC: 2627 AN: 4798

European-Finnish (FIN) AF: 0.529 AC: 5542 AN: 10470

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38021 AN: 67816

Other (OTH) AF: 0.605 AC: 1272 AN: 2102

Alfa AF: 0.587 Hom.: 3138

Bravo AF: 0.642

Asia WGS AF: 0.639 AC: 2223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
DANN	Benign	0.31
PhyloP100		-2.9
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: rs2741171; hg19: chr18-700687;