Variant 1-8861360-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001428.5(ENO1):c.1305A>G(p.Ter435=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,806 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 28 hom. )

Consequence

ENO1
NM_001428.5 stop_retained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.36

Variant links:

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]

ENO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-8861360-T-C is Benign according to our data. Variant chr1-8861360-T-C is described in ClinVar as [Benign]. Clinvar id is 722451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00143 (2088/1461518) while in subpopulation SAS AF= 0.0169 (1461/86238). AF 95% confidence interval is 0.0162. There are 28 homozygotes in gnomad4_exome. There are 1379 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ENO1	NM_001428.5 linkuse as main transcript	c.1305A>G	p.Ter435=	stop_retained_variant	12/12	ENST00000234590.10	NP_001419.1
ENO1	NM_001353346.3 linkuse as main transcript	c.1305A>G	p.Ter435=	stop_retained_variant	12/12		NP_001340275.1
ENO1	NM_001201483.4 linkuse as main transcript	c.1026A>G	p.Ter342=	stop_retained_variant	11/11		NP_001188412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENO1	ENST00000234590.10 linkuse as main transcript	c.1305A>G	p.Ter435=	stop_retained_variant	12/12	1	NM_001428.5	ENSP00000234590	P3	P06733-1
ENO1	ENST00000464920.2 linkuse as main transcript	n.2190A>G		non_coding_transcript_exon_variant	9/9	1
ENO1	ENST00000647408.1 linkuse as main transcript	c.1305A>G	p.Ter435=	stop_retained_variant	12/12			ENSP00000495530	A1
ENO1	ENST00000646370.2 linkuse as main transcript	c.*1058A>G		3_prime_UTR_variant, NMD_transcript_variant	13/13			ENSP00000495568

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00255

AC:

642

AN:

251440

Hom.:

AF XY:

0.00330

AC XY:

448

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000712

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00143

AC:

2088

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1379

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.000689

AC:

105

AN:

152288

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000419

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over