rs2612081

Positions:

• chr18-695030-G-A
• chr18-695030-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017512.7(ENOSF1):​c.310-696C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,026 control chromosomes in the GnomAD database, including 4,167 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 0.23 (4167 hom., cov: 32)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOSF1	NM_017512.7	c.310-696C>T		intron_variant		ENST00000647584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOSF1	ENST00000647584.2	c.310-696C>T		intron_variant			NM_017512.7	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34710 AN: 151908 Hom.: 4158 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00634

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.229 AC: 34754 AN: 152026 Hom.: 4167 Cov.: 32 AF XY: 0.226 AC XY: 16816 AN XY: 74304

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00655

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.199

Alfa AF: 0.211 Hom.: 1697

Bravo AF: 0.229

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2612081; hg19: chr18-695030;