rs2612101

Variant names:

• chr18-676473-C-T
• rs2612101
• NM_017512.7:c.1148+872G>A

Variant summary

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

The NM_001354067.2(ENOSF1):​c.1292+872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,092 control chromosomes in the GnomAD database, including 5,561 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 0.26 (5561 hom., cov: 32)
• Consequence: ENOSF1 NM_001354067.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• 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]

TYMS (HGNC:12441): (thymidylate synthetase) Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [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 (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354067.2. 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.1148+872G>A		intron	N/A	NP_059982.2
	ENOSF1	NM_001354067.2		c.1292+872G>A		intron	N/A	NP_001340996.1
	ENOSF1	NM_202758.5		c.1250+872G>A		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.1148+872G>A		intron	N/A	ENSP00000497230.2
	ENOSF1	ENST00000383578.7	TSL:1	c.902+872G>A		intron	N/A	ENSP00000373072.3
	ENOSF1	ENST00000581475.5	TSL:1	n.*535+872G>A		intron	N/A	ENSP00000464614.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39238 AN: 151974 Hom.: 5557 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.258 AC: 39278 AN: 152092 Hom.: 5561 Cov.: 32 AF XY: 0.253 AC XY: 18835 AN XY: 74348

African (AFR) AF: 0.343 AC: 14203 AN: 41466

American (AMR) AF: 0.281 AC: 4294 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.102 AC: 493 AN: 4810

European-Finnish (FIN) AF: 0.251 AC: 2657 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16379 AN: 67986

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.243 Hom.: 12771

Bravo AF: 0.264

Asia WGS AF: 0.0720 AC: 253 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	6.5
DANN	Benign	0.67
PhyloP100		0.68
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: rs2612101; hg19: chr18-676473;