rs2847326

Variant names:

• chr18-676228-T-A
• rs2847326
• NM_017512.7:c.1149-826A>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.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
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 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.1149-826A>T		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1293-826A>T		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1251-826A>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.1149-826A>T		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.903-826A>T		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*536-826A>T		intron	N/A	ENSP00000464614.1

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

African (AFR) AF: 0.285 AC: 11821 AN: 41484

American (AMR) AF: 0.277 AC: 4226 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.101 AC: 490 AN: 4828

European-Finnish (FIN) AF: 0.251 AC: 2657 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16419 AN: 67980

Other (OTH) AF: 0.215 AC: 454 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.30
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: rs2847326; hg19: chr18-676228;