rs766149401

Variant names:

Variant summary

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

The NM_203281.3(BMX):c.662A>G(p.Lys221Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,211,066 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 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: 24)

Exomes 𝑓: 0.000016 ( 0 hom. 6 hem. )

Consequence

BMX
NM_203281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Publications

0 publications found

Variant links:

Genes affected

BMX (HGNC:1079): (BMX non-receptor tyrosine kinase) This gene encodes a non-receptor tyrosine kinase belonging to the Tec kinase family. The protein contains a PH-like domain, which mediates membrane targeting by binding to phosphatidylinositol 3,4,5-triphosphate (PIP3), and a SH2 domain that binds to tyrosine-phosphorylated proteins and functions in signal transduction. The protein is implicated in several signal transduction pathways including the Stat pathway, and regulates differentiation and tumorigenicity of several types of cancer cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

BMX links:

ACE2 (HGNC:13557): (angiotensin converting enzyme 2) The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

ACE2 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=0.055983394).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMX	NM_203281.3 link	c.662A>G	p.Lys221Arg	missense_variant	Exon 7 of 19	ENST00000348343.11	NP_975010.1	P51813

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMX	ENST00000348343.11 link	c.662A>G	p.Lys221Arg	missense_variant	Exon 7 of 19	1	NM_203281.3	ENSP00000308774.6		P51813

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112955

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.000360

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

183167

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1098111

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363511

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30197

South Asian (SAS)

AF:

0.000166

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.000725

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000594

AC:

AN:

842040

Other (OTH)

AF:

0.0000217

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000177

AC:

AN:

112955

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

35101

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31108

American (AMR)

AF:

0.00

AC:

AN:

10688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.000360

AC:

AN:

2777

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53381

Other (OTH)

AF:

0.00

AC:

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.662A>G (p.K221R) alteration is located in exon 7 (coding exon 6) of the BMX gene. This alteration results from a A to G substitution at nucleotide position 662, causing the lysine (K) at amino acid position 221 to be replaced by an arginine (R). 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

0.066

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.11

T;T;T

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.62

.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N;N

PhyloP100

1.5

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.067

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.15

MVP

0.56

MPC

0.28

ClinPred

0.0079

GERP RS

2.4

Varity_R

0.073

gMVP

0.15

Mutation Taster

=99/1

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.

rs766149401

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over