X-149545740-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001171907.3(EOLA1):​c.110G>A​(p.Cys37Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 112,764 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

EOLA1
NM_001171907.3 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1534195).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EOLA1NM_001171907.3 linkuse as main transcriptc.110G>A p.Cys37Tyr missense_variant 4/5 ENST00000393985.8 NP_001165378.1 Q8TE69-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EOLA1ENST00000393985.8 linkuse as main transcriptc.110G>A p.Cys37Tyr missense_variant 4/51 NM_001171907.3 ENSP00000421745.1 Q8TE69-1

Frequencies

GnomAD3 genomes
AF:
0.00000887
AC:
1
AN:
112764
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34890
show subpopulations
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000887
AC:
1
AN:
112764
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34890
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsSep 01, 2021The c.110G>A (p.C37Y) alteration is located in exon 4 (coding exon 1) of the CXorf40A gene. This alteration results from a G to A substitution at nucleotide position 110, causing the cysteine (C) at amino acid position 37 to be replaced by a tyrosine (Y). 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
0.12
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
4.5
DANN
Benign
0.87
DEOGEN2
Benign
0.054
T;T;T;T;T;.;.;.;T
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.57
.;.;.;.;.;.;.;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Uncertain
2.3
M;M;M;M;M;M;M;M;M
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PROVEAN
Benign
-2.0
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.56
T;T;T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T;T
Polyphen
0.0010
B;B;B;B;B;.;.;.;B
Vest4
0.27
MutPred
0.42
Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);
MVP
0.13
MPC
1.8
ClinPred
1.0
D
GERP RS
1.5
Varity_R
0.14
gMVP
0.82

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.

Other links and lift over

dbSNP: rs1384851927; hg19: chrX-148627286; API