rs2847154

Variant names:

• chr18-687270-G-A
• rs2847154
• NM_017512.7:c.654-1262C>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.654-1262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,134 control chromosomes in the GnomAD database, including 3,393 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 0.20 (3392 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 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.654-1262C>T		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.798-1262C>T		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.798-1262C>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.654-1262C>T		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.408-1262C>T		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*41-1262C>T		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30675 AN: 152004 Hom.: 3388 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.500 AC: 6 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.202 AC: 30702 AN: 152122 Hom.: 3392 Cov.: 33 AF XY: 0.201 AC XY: 14922 AN XY: 74362

African (AFR) AF: 0.139 AC: 5775 AN: 41516

American (AMR) AF: 0.267 AC: 4077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3470

East Asian (EAS) AF: 0.00638 AC: 33 AN: 5174

South Asian (SAS) AF: 0.128 AC: 617 AN: 4824

European-Finnish (FIN) AF: 0.254 AC: 2686 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16373 AN: 67966

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.223 Hom.: 6014

Bravo AF: 0.200

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.066
DANN	Benign	0.63
PhyloP100		-1.8
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: rs2847154; hg19: chr18-687270;