Genetic Variant BBX:p.Ala260Val (chr3-107747993-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001142568.3(BBX):c.779C>T(p.Ala260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,314 control chromosomes in the GnomAD database, including 28 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 26 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.460

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003517747).

BP6

Variant 3-107747993-C-T is Benign according to our data. Variant chr3-107747993-C-T is described in ClinVar as [Benign]. Clinvar id is 773704.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBX	NM_001142568.3 link	c.779C>T	p.Ala260Val	missense_variant	Exon 9 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.779C>T	p.Ala260Val	missense_variant	Exon 9 of 18	1	NM_001142568.3	ENSP00000319974.8		Q8WY36-1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00242

AC:

606

AN:

250584

Hom.:

AF XY:

0.00306

AC XY:

415

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000901

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00190

AC:

2777

AN:

1461036

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1592

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000918

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152278

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.000895

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00261

AC:

317

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00197

EpiControl

AF:

0.00244

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 06, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

9.7

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;T;T;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.77

.;T;T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T;T;T

MetaSVM

Uncertain

0.70

MutationAssessor

Benign

0.34

N;.;N;N;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.28

T;T;T;D;T;T

Sift4G

Benign

0.36

T;T;T;T;T;T

Polyphen

0.050

B;B;B;.;.;B

Vest4

0.11

MVP

0.69

MPC

0.15

ClinPred

0.011

GERP RS

0.99

Varity_R

0.030

gMVP

0.19

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