1-8865352-G-A

Variant names:

• chr1-8865352-G-A
• rs563905264
• NM_001428.5:c.798C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001428.5(ENO1):​c.798C>T​(p.Asp266Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0000066 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENO1 NM_001428.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 0 publications found

Genes affected

ENO1 (HGNC:3350): (enolase 1) This gene encodes alpha-enolase, one of three enolase isoenzymes found in mammals. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001428.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	NM_001428.5	MANE Select	c.798C>T	p.Asp266Asp	synonymous	Exon 8 of 12	NP_001419.1	P06733-1
	ENO1	NM_001353346.3		c.798C>T	p.Asp266Asp	synonymous	Exon 8 of 12	NP_001340275.1	A0A2R8Y6G6
	ENO1	NM_001201483.4		c.519C>T	p.Asp173Asp	synonymous	Exon 7 of 11	NP_001188412.1	P06733-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	ENST00000234590.10	TSL:1 MANE Select	c.798C>T	p.Asp266Asp	synonymous	Exon 8 of 12	ENSP00000234590.4	P06733-1
	ENO1	ENST00000464920.2	TSL:1	n.1683C>T		non_coding_transcript_exon	Exon 5 of 9
	ENO1	ENST00000879697.1		c.828C>T	p.Asp276Asp	synonymous	Exon 8 of 12	ENSP00000549756.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000656 AC: 1 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.9
DANN	Benign	0.92
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs563905264; hg19: chr1-8925411;