Variant X-103063145-A-C 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.130T>G(p.Cys44Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,210,140 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.510

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=0.04196635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEX1	NM_018476.4 linkuse as main transcript	c.130T>G	p.Cys44Gly	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.130T>G	p.Cys44Gly	missense_variant	3/3	1	NM_018476.4	ENSP00000361813	P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111872

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34044

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:

0.000566

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:

183330

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000216

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:

0.00000182

AC:

AN:

1098268

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

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:

0.0000179

AC:

AN:

111872

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34044

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000566

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Apr 01, 2024

The c.130T>G (p.C44G) alteration is located in exon 3 (coding exon 1) of the BEX1 gene. This alteration results from a T to G substitution at nucleotide position 130, causing the cysteine (C) at amino acid position 44 to be replaced by a glycine (G). 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

0.085

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.1

DANN

Benign

0.70

DEOGEN2

Benign

0.26

FATHMM_MKL

Benign

0.00046

LIST_S2

Benign

0.48

M_CAP

Benign

0.0040

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

REVEL

Benign

0.033

Sift

Benign

0.33

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.12

MutPred

0.52

Gain of disorder (P = 0.0256);

MVP

0.068

MPC

0.084

ClinPred

0.024

GERP RS

-2.0

Varity_R

0.071

gMVP

0.072

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