rs2790

Variant names:

• chr18-673086-A-G
• rs2790
• NM_017512.7:c.*1219T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-673086-A-G
• chr18-673086-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017512.7(ENOSF1):​c.*1219T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,377,150 control chromosomes in the GnomAD database, including 34,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4066 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30107 hom.)
• Consequence: ENOSF1 NM_017512.7 3_prime_UTR
• Scores: Splicing: ADA: 0.00003376
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.707
• Publications: 56 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-673086-A-G is Benign according to our data. Variant chr18-673086-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.*1219T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2
TYMS	NM_001071.4	c.*89A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000323274.15	NP_001062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOSF1	ENST00000647584.2	c.*1219T>C		3_prime_UTR_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2
TYMS	ENST00000323274.15	c.*89A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001071.4	ENSP00000315644.10

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34419 AN: 152052 Hom.: 4065 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.217 AC: 265510 AN: 1224980 Hom.: 30107 Cov.: 19 AF XY: 0.220 AC XY: 131461 AN XY: 596762

African (AFR) AF: 0.260 AC: 7393 AN: 28418

American (AMR) AF: 0.225 AC: 6435 AN: 28588

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 4436 AN: 18206

East Asian (EAS) AF: 0.389 AC: 14733 AN: 37844

South Asian (SAS) AF: 0.356 AC: 16422 AN: 46122

European-Finnish (FIN) AF: 0.165 AC: 7182 AN: 43442

Middle Eastern (MID) AF: 0.335 AC: 1628 AN: 4854

European-Non Finnish (NFE) AF: 0.202 AC: 195562 AN: 967986

Other (OTH) AF: 0.237 AC: 11719 AN: 49520

GnomAD4 genome AF: 0.226 AC: 34437 AN: 152170 Hom.: 4066 Cov.: 32 AF XY: 0.229 AC XY: 17064 AN XY: 74394

African (AFR) AF: 0.250 AC: 10374 AN: 41508

American (AMR) AF: 0.217 AC: 3311 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 887 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1909 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1712 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1738 AN: 10606

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13869 AN: 67994

Other (OTH) AF: 0.241 AC: 506 AN: 2102

Alfa AF: 0.219 Hom.: 5778

Bravo AF: 0.231

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24997136) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.47
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.010
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: rs2790; hg19: chr18-673086;