Variant X-149546949-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000393985.8(EOLA1):c.464G>A(p.Gly155Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,201,760 control chromosomes in the GnomAD database, including 1 homozygotes. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 12 hem., cov: 19)

Exomes 𝑓: 0.000059 ( 1 hom. 20 hem. )

Consequence

EOLA1
ENST00000393985.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.528

Variant links:

Genes affected

EOLA1 (HGNC:28089): (endothelium and lymphocyte associated ASCH domain 1) Involved in regulation of interleukin-6 production. [provided by Alliance of Genome Resources, Apr 2022]

EOLA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014489055).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EOLA1	NM_001171907.3 linkuse as main transcript	c.464G>A	p.Gly155Glu	missense_variant	5/5	ENST00000393985.8	NP_001165378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EOLA1	ENST00000393985.8 linkuse as main transcript	c.464G>A	p.Gly155Glu	missense_variant	5/5	1	NM_001171907.3	ENSP00000421745	P1	Q8TE69-1

Frequencies

GnomAD3 genomes

AF:

0.000405

AC:

AN:

108731

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

AN XY:

31069

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000692

GnomAD3 exomes

AF:

0.000108

AC:

AN:

120426

Hom.:

AF XY:

0.0000546

AC XY:

AN XY:

36638

show subpopulations

Gnomad AFR exome

AF:

0.000917

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000586

AC:

AN:

1092980

Hom.:

Cov.:

AF XY:

0.0000557

AC XY:

AN XY:

358846

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.000145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000404

AC:

AN:

108780

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

AN XY:

31130

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000684

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000601

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000145

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.464G>A (p.G155E) alteration is located in exon 5 (coding exon 2) of the CXorf40A gene. This alteration results from a G to A substitution at nucleotide position 464, causing the glycine (G) at amino acid position 155 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

DANN

Benign

0.59

DEOGEN2

Benign

0.0072

T;T;T;T;T;.;T

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.42

.;.;.;.;.;T;T

M_CAP

Benign

0.00073

MetaRNN

Benign

0.014

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.075

N;N;N;N;N;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PROVEAN

Benign

0.70

N;N;N;N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.21

T;T;T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T;T;T

Polyphen

0.0040

B;B;B;B;B;.;B

Vest4

0.042

MVP

0.068

MPC

1.5

ClinPred

0.0052

GERP RS

-2.5

Varity_R

0.080

gMVP

0.54

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