rs2612100

Variant names:

• chr18-672363-G-A
• rs2612100
• NM_017512.7:c.*1942C>T

Variant summary

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

The NM_017512.7(ENOSF1):​c.*1942C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,122 control chromosomes in the GnomAD database, including 15,317 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 0.42 (15305 hom., cov: 32)
  • Exomes 𝑓: 0.35 (12 hom.)
• Consequence: ENOSF1 NM_017512.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.*1942C>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2
TYMS	NM_001071.4	c.805-497G>A		intron_variant	Intron 6 of 6	ENST00000323274.15	NP_001062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.*1942C>T		3_prime_UTR_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2
TYMS	ENST00000323274.15	c.805-497G>A		intron_variant	Intron 6 of 6	1	NM_001071.4	ENSP00000315644.10

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64128 AN: 151832 Hom.: 15279 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.349 AC: 60 AN: 172 Hom.: 12 Cov.: 0 AF XY: 0.411 AC XY: 37 AN XY: 90

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.267 AC: 8 AN: 30

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 3 AN: 6

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.323 AC: 40 AN: 124

Other (OTH) AF: 0.625 AC: 5 AN: 8

GnomAD4 genome AF: 0.422 AC: 64189 AN: 151950 Hom.: 15305 Cov.: 32 AF XY: 0.425 AC XY: 31565 AN XY: 74256

African (AFR) AF: 0.639 AC: 26452 AN: 41426

American (AMR) AF: 0.345 AC: 5254 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3468

East Asian (EAS) AF: 0.685 AC: 3546 AN: 5180

South Asian (SAS) AF: 0.447 AC: 2150 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3198 AN: 10534

Middle Eastern (MID) AF: 0.476 AC: 138 AN: 290

European-Non Finnish (NFE) AF: 0.310 AC: 21051 AN: 67970

Other (OTH) AF: 0.420 AC: 885 AN: 2108

Alfa AF: 0.370 Hom.: 2010

Bravo AF: 0.435

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.033
DANN	Benign	0.36
PhyloP100		-2.1
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: rs2612100; hg19: chr18-672363;