NM_017512.7:c.1230+321G>A

Variant names:

• chr18-675000-C-T
• rs9948583
• NM_017512.7:c.1230+321G>A

Variant summary

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

The NM_017512.7(ENOSF1):​c.1230+321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,038 control chromosomes in the GnomAD database, including 13,087 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 0.40 (13087 hom., cov: 33)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.1230+321G>A		intron_variant	Intron 15 of 15	ENST00000647584.2	NP_059982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.1230+321G>A		intron_variant	Intron 15 of 15		NM_017512.7	ENSP00000497230.2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60563 AN: 151920 Hom.: 13074 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.399 AC: 60607 AN: 152038 Hom.: 13087 Cov.: 33 AF XY: 0.401 AC XY: 29815 AN XY: 74314

African (AFR) AF: 0.548 AC: 22705 AN: 41464

American (AMR) AF: 0.335 AC: 5121 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3469 AN: 5168

South Asian (SAS) AF: 0.458 AC: 2205 AN: 4814

European-Finnish (FIN) AF: 0.303 AC: 3202 AN: 10560

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21419 AN: 67962

Other (OTH) AF: 0.406 AC: 859 AN: 2114

Alfa AF: 0.338 Hom.: 14773

Bravo AF: 0.407

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.23
PhyloP100		-0.61
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: rs9948583; hg19: chr18-675000;