rs754901525

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142568.3(BBX):c.169C>A(p.Leu57Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 publications found

Variant links:

Genes affected

BBX (HGNC:14422): (BBX high mobility group box domain containing) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BBX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25327444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBX	NM_001142568.3 link	c.169C>A	p.Leu57Ile	missense_variant	Exon 5 of 18	ENST00000325805.13	NP_001136040.1	Q8WY36-1A8K6U2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13 link	c.169C>A	p.Leu57Ile	missense_variant	Exon 5 of 18	1	NM_001142568.3	ENSP00000319974.8		Q8WY36-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250804

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726824

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111470

Other (OTH)

AF:

0.0000331

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.169C>A (p.L57I) alteration is located in exon 5 (coding exon 2) of the BBX gene. This alteration results from a C to A substitution at nucleotide position 169, causing the leucine (L) at amino acid position 57 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

.;T;T;.;.;T;T;.;T;T;.;.;.;T;.;T;.

Eigen

Benign

0.054

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

.;D;D;D;D;T;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

0.97

L;.;L;.;L;.;.;.;.;.;.;L;.;.;.;.;.

PhyloP100

4.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.47

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

D;D;D;D;D;D;D;D;D;D;D;D;D;D;T;D;T

Sift4G

Benign

0.14

T;T;T;T;D;D;T;T;T;T;T;T;T;T;T;D;T

Polyphen

0.81

P;P;P;.;.;.;.;.;.;.;.;P;.;.;.;.;.

Vest4

0.36

MutPred

0.30

Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);.;Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);Loss of glycosylation at K54 (P = 0.0575);

MVP

0.44

MPC

0.42

ClinPred

0.48

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.094

gMVP

0.11

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

rs754901525

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over