Variant X-103063225-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018476.4(BEX1):c.50C>A(p.Ala17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,209,237 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A17V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.159

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]

BEX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042336047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEX1	NM_018476.4 linkuse as main transcript	c.50C>A	p.Ala17Asp	missense_variant	3/3	ENST00000372728.4	NP_060946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEX1	ENST00000372728.4 linkuse as main transcript	c.50C>A	p.Ala17Asp	missense_variant	3/3	1	NM_018476.4	ENSP00000361813	P1

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111234

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33450

show subpopulations

Gnomad AFR

AF:

0.0000982

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182447

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67241

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1098003

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363359

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111234

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33450

show subpopulations

Gnomad4 AFR

AF:

0.0000982

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

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 27, 2022

The c.50C>A (p.A17D) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a C to A substitution at nucleotide position 50, causing the alanine (A) at amino acid position 17 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.8

DANN

Benign

0.84

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.16

M_CAP

Benign

0.021

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.024

Sift

Benign

0.11

Sift4G

Benign

0.084

Polyphen

0.0

Vest4

0.14

MutPred

0.39

Gain of helix (P = 0.062);

MVP

0.068

MPC

0.10

ClinPred

0.010

GERP RS

0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.31

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