rs11280056

Variant names:

• chr18-673443-TTTAAAG-T
• rs11280056
• NM_017512.7:c.*856_*861delCTTTAA

Your query was ambiguous. Multiple possible variants found:

• chr18-673443-TTTAAAG-T
• chr18-673443-TTTAAAG-TTTAAAGTTAAAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_017512.7(ENOSF1):​c.*856_*861delCTTTAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 217,316 control chromosomes in the GnomAD database, including 17,511 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (12782 hom., cov: 0)
  • Exomes 𝑓: 0.36 (4729 hom.)
• Consequence: ENOSF1 NM_017512.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 33 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOSF1	NM_017512.7	c.*856_*861delCTTTAA		3_prime_UTR_variant	Exon 16 of 16	ENST00000647584.2	NP_059982.2
TYMS	NM_001071.4	c.*450_*455delAAGTTA		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.*856_*861delCTTTAA		3_prime_UTR_variant	Exon 16 of 16		NM_017512.7	ENSP00000497230.2
TYMS	ENST00000323274.15	c.*450_*455delAAGTTA		3_prime_UTR_variant	Exon 7 of 7	1	NM_001071.4	ENSP00000315644.10

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59744 AN: 151380 Hom.: 12769 Cov.: 0

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.358 AC: 23543 AN: 65816 Hom.: 4729 AF XY: 0.354 AC XY: 10768 AN XY: 30388

African (AFR) AF: 0.525 AC: 1508 AN: 2874

American (AMR) AF: 0.289 AC: 672 AN: 2322

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1483 AN: 4106

East Asian (EAS) AF: 0.633 AC: 5735 AN: 9064

South Asian (SAS) AF: 0.416 AC: 266 AN: 640

European-Finnish (FIN) AF: 0.250 AC: 14 AN: 56

Middle Eastern (MID) AF: 0.458 AC: 176 AN: 384

European-Non Finnish (NFE) AF: 0.290 AC: 11891 AN: 41016

Other (OTH) AF: 0.336 AC: 1798 AN: 5354

GnomAD4 genome AF: 0.395 AC: 59790 AN: 151500 Hom.: 12782 Cov.: 0 AF XY: 0.398 AC XY: 29482 AN XY: 74028

African (AFR) AF: 0.547 AC: 22575 AN: 41276

American (AMR) AF: 0.333 AC: 5077 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3466

East Asian (EAS) AF: 0.680 AC: 3461 AN: 5090

South Asian (SAS) AF: 0.445 AC: 2139 AN: 4804

European-Finnish (FIN) AF: 0.301 AC: 3168 AN: 10532

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20869 AN: 67798

Other (OTH) AF: 0.398 AC: 835 AN: 2096

Alfa AF: 0.346 Hom.: 1165

Bravo AF: 0.406

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11280056; hg19: chr18-673443; COSMIC: COSV51891993; COSMIC: COSV51891993;