chr18-680838-G-A

Variant names:

• chr18-680838-G-A
• rs7236747
• NM_017512.7:c.877-2101C>T

Variant summary

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

The NM_017512.7(ENOSF1):​c.877-2101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 149,204 control chromosomes in the GnomAD database, including 12,145 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 0.39 (12145 hom., cov: 26)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 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.877-2101C>T		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1021-2101C>T		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1020+2408C>T		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.877-2101C>T		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.631-2101C>T		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*264-2101C>T		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 57604 AN: 149088 Hom.: 12118 Cov.: 26

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.386 AC: 57659 AN: 149204 Hom.: 12145 Cov.: 26 AF XY: 0.385 AC XY: 28000 AN XY: 72740

African (AFR) AF: 0.563 AC: 22807 AN: 40492

American (AMR) AF: 0.319 AC: 4785 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1327 AN: 3446

East Asian (EAS) AF: 0.449 AC: 2274 AN: 5062

South Asian (SAS) AF: 0.425 AC: 1988 AN: 4678

European-Finnish (FIN) AF: 0.241 AC: 2387 AN: 9916

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 20979 AN: 67350

Other (OTH) AF: 0.396 AC: 821 AN: 2074

Alfa AF: 0.329 Hom.: 1090

Bravo AF: 0.398

Asia WGS AF: 0.482 AC: 1673 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.54
DANN	Benign	0.31
PhyloP100		-0.49
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: rs7236747; hg19: chr18-680838;