Variant X-149933793-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001013845.2(EOLA2):c.82C>T(p.Arg28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,199,417 control chromosomes in the GnomAD database, including 3 homozygotes. There are 84 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 6 hem., cov: 21)

Exomes 𝑓: 0.00018 ( 3 hom. 78 hem. )

Consequence

EOLA2
NM_001013845.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

EOLA2 (HGNC:17402): (endothelium and lymphocyte associated ASCH domain 2)

EOLA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096200466).

BP6

Variant X-149933793-G-A is Benign according to our data. Variant chrX-149933793-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2661628.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EOLA2	NM_001013845.2 linkuse as main transcript	c.82C>T	p.Arg28Cys	missense_variant	4/5	ENST00000370406.8	NP_001013867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EOLA2	ENST00000370406.8 linkuse as main transcript	c.82C>T	p.Arg28Cys	missense_variant	4/5	1	NM_001013845.2	ENSP00000359434	P1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

109794

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

AN XY:

32812

show subpopulations

Gnomad AFR

AF:

0.000452

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000944

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000281

AC:

AN:

181534

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

66288

show subpopulations

Gnomad AFR exome

AF:

0.000237

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000585

Gnomad FIN exome

AF:

0.000376

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000184

AC:

201

AN:

1089576

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

AN XY:

355742

show subpopulations

Gnomad4 AFR exome

AF:

0.000433

Gnomad4 AMR exome

AF:

0.0000856

Gnomad4 ASJ exome

AF:

0.00228

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000692

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.0000933

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000237

AC:

AN:

109841

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

AN XY:

32871

show subpopulations

Gnomad4 AFR

AF:

0.000451

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00226

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000944

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000348

Hom.:

ExAC

AF:

0.000240

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.82C>T (p.R28C) alteration is located in exon 4 (coding exon 1) of the CXorf40B gene. This alteration results from a C to T substitution at nucleotide position 82, causing the arginine (R) at amino acid position 28 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

EOLA2: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T;T;.;.

FATHMM_MKL

Benign

0.013

LIST_S2

Uncertain

0.94

D;.;.;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.096

T;T;T;T;T;T

MetaSVM

Uncertain

0.48

MutationAssessor

Uncertain

2.6

.;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Pathogenic

-6.7

D;D;D;D;.;.

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;.;.

Polyphen

1.0

.;D;D;D;.;.

Vest4

0.33

MVP

0.76

MPC

0.84

ClinPred

0.18

GERP RS

1.7

Varity_R

0.55

gMVP

0.76

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