Genetic Variant NM_018476.4:c.251G>A (chrX-103063024-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018476.4(BEX1):c.251G>A(p.Arg84Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,209,322 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., 18 hem., cov: 22)

Exomes 𝑓: 0.000053 ( 0 hom. 18 hem. )

Consequence

BEX1
NM_018476.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068727136).

BS2

High Hemizygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018476.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEX1	NM_018476.4	MANE Select	c.251G>A	p.Arg84Lys	missense	Exon 3 of 3	NP_060946.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BEX1	ENST00000372728.4	TSL:1 MANE Select	c.251G>A	p.Arg84Lys	missense	Exon 3 of 3	ENSP00000361813.3	Q9HBH7
BEX1	ENST00000885580.1		c.251G>A	p.Arg84Lys	missense	Exon 2 of 2	ENSP00000555639.1
BEX1	ENST00000885581.1		c.251G>A	p.Arg84Lys	missense	Exon 2 of 2	ENSP00000555640.1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

111003

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00177

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

GnomAD2 exomes

AF:

0.000153

AC:

AN:

183532

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000528

AC:

AN:

1098265

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

363619

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

26403

American (AMR)

AF:

0.000170

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000237

AC:

AN:

842148

Other (OTH)

AF:

0.0000651

AC:

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000486

AC:

AN:

111057

Hom.:

Cov.:

AF XY:

0.000542

AC XY:

AN XY:

33231

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

30552

American (AMR)

AF:

0.00

AC:

AN:

10434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3497

South Asian (SAS)

AF:

0.00

AC:

AN:

2621

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52984

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

FATHMM_MKL

Benign

0.00070

LIST_S2

Benign

0.66

M_CAP

Benign

0.032

MetaRNN

Benign

0.0069

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

0.26

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Benign

0.28

Sift4G

Benign

0.59

Polyphen

0.026

Vest4

0.28

MVP

0.13

MPC

0.12

ClinPred

0.027

GERP RS

1.4

Varity_R

0.10

gMVP

0.43

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over