Variant X-149933852-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001013845.2(EOLA2):c.23T>C(p.Phe8Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,200,752 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 7 hem., cov: 21)

Exomes 𝑓: 0.000032 ( 0 hom. 15 hem. )

Consequence

EOLA2
NM_001013845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EOLA2	NM_001013845.2 linkuse as main transcript	c.23T>C	p.Phe8Ser	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.23T>C	p.Phe8Ser	missense_variant	4/5	1	NM_001013845.2	ENSP00000359434	P1

Frequencies

GnomAD3 genomes

AF:

0.000209

AC:

AN:

110265

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

33101

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00207

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:

0.000673

GnomAD3 exomes

AF:

0.000101

AC:

AN:

178496

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

63932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000634

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:

0.000228

GnomAD4 exome

AF:

0.0000321

AC:

AN:

1090443

Hom.:

Cov.:

AF XY:

0.0000420

AC XY:

AN XY:

357055

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000944

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:

0.0000437

GnomAD4 genome

AF:

0.000209

AC:

AN:

110309

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

33157

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00206

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:

0.000665

Bravo

AF:

0.000242

ExAC

AF:

0.00000825

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 15, 2021

The c.23T>C (p.F8S) alteration is located in exon 4 (coding exon 1) of the CXorf40B gene. This alteration results from a T to C substitution at nucleotide position 23, causing the phenylalanine (F) at amino acid position 8 to be replaced by a serine (S). 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

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T;T;.;.

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.84

T;.;.;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D

MetaSVM

Uncertain

0.65

MutationAssessor

Uncertain

2.8

.;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Pathogenic

-6.5

D;D;D;D;.;.

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0010

D;D;D;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;.;.

Polyphen

1.0

.;D;D;D;.;.

Vest4

0.87

MutPred

0.74

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.89

MPC

1.9

ClinPred

0.77

GERP RS

2.4

Varity_R

0.89

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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