18-679637-T-C

Variant names:

• chr18-679637-T-C
• rs2847324
• NM_017512.7:c.877-900A>G

Variant summary

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

The NM_001354067.2(ENOSF1):​c.1021-900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,724 control chromosomes in the GnomAD database, including 4,574 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 (4574 hom., cov: 31)
• Consequence: ENOSF1 NM_001354067.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354067.2. 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.877-900A>G		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1021-900A>G		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1021-1765A>G		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.877-900A>G		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.631-900A>G		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*264-900A>G		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36075 AN: 151612 Hom.: 4565 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.238 AC: 36123 AN: 151724 Hom.: 4574 Cov.: 31 AF XY: 0.234 AC XY: 17361 AN XY: 74120

African (AFR) AF: 0.271 AC: 11190 AN: 41362

American (AMR) AF: 0.277 AC: 4215 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.00369 AC: 19 AN: 5150

South Asian (SAS) AF: 0.101 AC: 484 AN: 4810

European-Finnish (FIN) AF: 0.249 AC: 2612 AN: 10484

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16404 AN: 67892

Other (OTH) AF: 0.213 AC: 449 AN: 2108

Alfa AF: 0.255 Hom.: 738

Bravo AF: 0.242

Asia WGS AF: 0.0630 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.87
DANN	Benign	0.36
PhyloP100		-0.44
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: rs2847324; hg19: chr18-679637;