chr18-674440-A-C

Variant names:

• chr18-674440-A-C
• rs11081251
• NM_017512.7:c.1231-34T>G

Variant summary

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

The NM_017512.7(ENOSF1):​c.1231-34T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,370,686 control chromosomes in the GnomAD database, including 83,142 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 0.36 (10184 hom., cov: 32)
  • Exomes 𝑓: 0.34 (72958 hom.)
• Consequence: ENOSF1 NM_017512.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 15 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 = 0.666 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.1231-34T>G		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1375-34T>G		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1333-34T>G		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.1231-34T>G		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.985-34T>G		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*618-34T>G		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54141 AN: 151902 Hom.: 10177 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.373 AC: 84878 AN: 227544 AF XY: 0.375

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.696

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.339 AC: 413541 AN: 1218666 Hom.: 72958 Cov.: 16 AF XY: 0.343 AC XY: 211847 AN XY: 617474

African (AFR) AF: 0.427 AC: 11785 AN: 27570

American (AMR) AF: 0.321 AC: 12233 AN: 38114

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 9234 AN: 23724

East Asian (EAS) AF: 0.669 AC: 25505 AN: 38134

South Asian (SAS) AF: 0.443 AC: 34183 AN: 77224

European-Finnish (FIN) AF: 0.302 AC: 15915 AN: 52744

Middle Eastern (MID) AF: 0.483 AC: 2504 AN: 5188

European-Non Finnish (NFE) AF: 0.313 AC: 283179 AN: 903896

Other (OTH) AF: 0.365 AC: 19003 AN: 52072

GnomAD4 genome AF: 0.356 AC: 54168 AN: 152020 Hom.: 10184 Cov.: 32 AF XY: 0.361 AC XY: 26856 AN XY: 74302

African (AFR) AF: 0.408 AC: 16914 AN: 41446

American (AMR) AF: 0.322 AC: 4914 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1376 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3536 AN: 5164

South Asian (SAS) AF: 0.446 AC: 2144 AN: 4808

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10562

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20998 AN: 67978

Other (OTH) AF: 0.372 AC: 782 AN: 2104

Alfa AF: 0.340 Hom.: 23511

Bravo AF: 0.360

Asia WGS AF: 0.569 AC: 1979 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	13
DANN	Benign	0.27
PhyloP100		-0.039
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs11081251; hg19: chr18-674440; COSMIC: COSV107232459; COSMIC: COSV107232459;