X-103062959-G-A

Variant names:

• chrX-103062959-G-A
• rs148308204
• NM_018476.4:c.316C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.213
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.120794535).
• BS2: High Hemizygotes in GnomAd4 at 9 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.316C>T	p.Arg106Trp	missense	Exon 3 of 3	NP_060946.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEX1	ENST00000372728.4	TSL:1 MANE Select	c.316C>T	p.Arg106Trp	missense	Exon 3 of 3	ENSP00000361813.3	Q9HBH7
	BEX1	ENST00000885580.1		c.316C>T	p.Arg106Trp	missense	Exon 2 of 2	ENSP00000555639.1
	BEX1	ENST00000885581.1		c.316C>T	p.Arg106Trp	missense	Exon 2 of 2	ENSP00000555640.1

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 22 AN: 111075 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.000169 AC: 31 AN: 183497 AF XY: 0.000191

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 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

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.000280 AC: 236 AN: 842128

Other (OTH) AF: 0.0000868 AC: 4 AN: 46097

GnomAD4 genome AF: 0.000198 AC: 22 AN: 111075 Hom.: 0 Cov.: 22 AF XY: 0.000270 AC XY: 9 AN XY: 33281

African (AFR) AF: 0.0000328 AC: 1 AN: 30508

American (AMR) AF: 0.0000958 AC: 1 AN: 10435

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3525

South Asian (SAS) AF: 0.00 AC: 0 AN: 2636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.000378 AC: 20 AN: 52980

Other (OTH) AF: 0.00 AC: 0 AN: 1494

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.21
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

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