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GeneBe

X-103062959-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018476.4(BEX1):c.316C>T(p.Arg106Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,209,316 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 9 hem., cov: 22)
Exomes 𝑓: 0.00022 ( 0 hom. 80 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.213
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.120794535).
BS2
High Hemizygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BEX1NM_018476.4 linkuse as main transcriptc.316C>T p.Arg106Trp missense_variant 3/3 ENST00000372728.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BEX1ENST00000372728.4 linkuse as main transcriptc.316C>T p.Arg106Trp missense_variant 3/31 NM_018476.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000198
AC:
22
AN:
111075
Hom.:
0
Cov.:
22
AF XY:
0.000270
AC XY:
9
AN XY:
33281
show subpopulations
Gnomad AFR
AF:
0.0000328
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000958
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:
0.000378
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000169
AC:
31
AN:
183497
Hom.:
0
AF XY:
0.000191
AC XY:
13
AN XY:
67927
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
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:
0.000366
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000220
AC:
242
AN:
1098241
Hom.:
0
Cov.:
31
AF XY:
0.000220
AC XY:
80
AN XY:
363597
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
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:
0.000280
Gnomad4 OTH exome
AF:
0.0000868
GnomAD4 genome
AF:
0.000198
AC:
22
AN:
111075
Hom.:
0
Cov.:
22
AF XY:
0.000270
AC XY:
9
AN XY:
33281
show subpopulations
Gnomad4 AFR
AF:
0.0000328
Gnomad4 AMR
AF:
0.0000958
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000378
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000340
Hom.:
0
Bravo
AF:
0.000174
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000346
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000297
AC:
2
ExAC
AF:
0.000206
AC:
25
EpiCase
AF:
0.000218
EpiControl
AF:
0.000593

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 GeneticsMay 16, 2022The c.316C>T (p.R106W) 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 316, causing the arginine (R) at amino acid position 106 to be replaced by a tryptophan (W). 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
0.14
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
14
Dann
Uncertain
0.98
DEOGEN2
Benign
0.33
T
FATHMM_MKL
Benign
0.00095
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-5.8
D
REVEL
Benign
0.17
Sift
Benign
0.059
T
Sift4G
Benign
0.086
T
Polyphen
0.14
B
Vest4
0.32
MVP
0.30
MPC
0.084
ClinPred
0.17
T
GERP RS
2.4
Varity_R
0.26
gMVP
0.35

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: rs148308204; hg19: chrX-102317887; COSMIC: COSV65580771; API