rs2298582

Variant names:

• chr18-677621-T-G
• rs2298582
• NM_017512.7:c.1048+122A>C

Variant summary

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

The NM_017512.7(ENOSF1):​c.1048+122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,375,018 control chromosomes in the GnomAD database, including 7,142 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 0.091 (718 hom., cov: 33)
  • Exomes 𝑓: 0.10 (6424 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.1048+122A>C		intron_variant	Intron 13 of 15	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1048+122A>C		intron_variant	Intron 13 of 15		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13857 AN: 151690 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0997 AC: 121948 AN: 1223210 Hom.: 6424 Cov.: 17 AF XY: 0.0998 AC XY: 60457 AN XY: 605826

African (AFR) AF: 0.0671 AC: 1829 AN: 27252

American (AMR) AF: 0.0609 AC: 1669 AN: 27406

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 2556 AN: 19206

East Asian (EAS) AF: 0.0741 AC: 2789 AN: 37652

South Asian (SAS) AF: 0.0806 AC: 5237 AN: 64960

European-Finnish (FIN) AF: 0.0698 AC: 2997 AN: 42934

Middle Eastern (MID) AF: 0.117 AC: 408 AN: 3478

European-Non Finnish (NFE) AF: 0.105 AC: 99289 AN: 948710

Other (OTH) AF: 0.100 AC: 5174 AN: 51612

GnomAD4 genome AF: 0.0913 AC: 13857 AN: 151808 Hom.: 718 Cov.: 33 AF XY: 0.0903 AC XY: 6703 AN XY: 74228

African (AFR) AF: 0.0683 AC: 2823 AN: 41304

American (AMR) AF: 0.0825 AC: 1259 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.0794 AC: 409 AN: 5152

South Asian (SAS) AF: 0.0892 AC: 428 AN: 4796

European-Finnish (FIN) AF: 0.0744 AC: 786 AN: 10562

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7334 AN: 67942

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.103 Hom.: 2516

Bravo AF: 0.0893

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.42
PhyloP100		-0.092
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: rs2298582; hg19: chr18-677621;