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GeneBe

X-103063171-G-A

Variant summary

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

The NM_018476.4(BEX1):c.104C>T(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,209,789 control chromosomes in the GnomAD database, including 1 homozygotes. There are 179 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 0.00022 ( 0 hom., 3 hem., cov: 22)
Exomes 𝑓: 0.00044 ( 1 hom. 176 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

4
13

Clinical Significance

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

Conservation

PhyloP100: 0.493
Variant links:
Genes affected
BEX1 (HGNC:1036): (brain expressed X-linked 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity. Involved in positive regulation of DNA-binding transcription factor activity and positive regulation of transcription by RNA polymerase II. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0876317).
BP6
Variant X-103063171-G-A is Benign according to our data. Variant chrX-103063171-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2454286.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
High Hemizygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BEX1NM_018476.4 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 3/3 ENST00000372728.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BEX1ENST00000372728.4 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 3/31 NM_018476.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000215
AC:
24
AN:
111536
Hom.:
0
Cov.:
22
AF XY:
0.0000890
AC XY:
3
AN XY:
33726
show subpopulations
Gnomad AFR
AF:
0.0000652
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000951
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:
0.000377
Gnomad OTH
AF:
0.000668
GnomAD3 exomes
AF:
0.000218
AC:
40
AN:
183199
Hom.:
0
AF XY:
0.000251
AC XY:
17
AN XY:
67697
show subpopulations
Gnomad AFR exome
AF:
0.0000760
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.000134
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000314
Gnomad FIN exome
AF:
0.0000625
Gnomad NFE exome
AF:
0.000355
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.000444
AC:
488
AN:
1098201
Hom.:
1
Cov.:
31
AF XY:
0.000484
AC XY:
176
AN XY:
363555
show subpopulations
Gnomad4 AFR exome
AF:
0.0000758
Gnomad4 AMR exome
AF:
0.0000852
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000332
Gnomad4 FIN exome
AF:
0.000148
Gnomad4 NFE exome
AF:
0.000493
Gnomad4 OTH exome
AF:
0.000781
GnomAD4 genome
AF:
0.000215
AC:
24
AN:
111588
Hom.:
0
Cov.:
22
AF XY:
0.0000888
AC XY:
3
AN XY:
33788
show subpopulations
Gnomad4 AFR
AF:
0.0000651
Gnomad4 AMR
AF:
0.0000949
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000377
Gnomad4 OTH
AF:
0.000660
Alfa
AF:
0.000379
Hom.:
15
Bravo
AF:
0.000174
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00138
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000297
AC:
2
ExAC
AF:
0.000247
AC:
30
EpiCase
AF:
0.000709
EpiControl
AF:
0.000474

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 submitterclinical testingAmbry GeneticsFeb 23, 2023The c.104C>T (p.A35V) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a C to T substitution at nucleotide position 104, causing the alanine (A) at amino acid position 35 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023BEX1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.62
Cadd
Benign
16
Dann
Uncertain
1.0
DEOGEN2
Benign
0.35
T
FATHMM_MKL
Benign
0.0010
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.088
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.12
Sift
Benign
0.061
T
Sift4G
Uncertain
0.024
D
Polyphen
0.94
P
Vest4
0.044
MVP
0.29
MPC
0.088
ClinPred
0.063
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.073
gMVP
0.24

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.

Other links and lift over

dbSNP: rs140998909; hg19: chrX-102318099; API