rs117452684

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017637.6(BNC2):c.2768C>T(p.Ala923Val) variant causes a missense change. The variant allele was found at a frequency of 0.0295 in 1,614,110 control chromosomes in the GnomAD database, including 848 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 34 hom., cov: 31)

Exomes 𝑓: 0.031 ( 814 hom. )

Consequence

BNC2
NM_017637.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 4.83

Variant links:

Genes affected

BNC2 (HGNC:30988): (basonuclin zinc finger protein 2) This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]

BNC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004229605).

BP6

Variant 9-16419521-G-A is Benign according to our data. Variant chr9-16419521-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 120238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-16419521-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2941/152246) while in subpopulation NFE AF= 0.0323 (2199/68012). AF 95% confidence interval is 0.0312. There are 34 homozygotes in gnomad4. There are 1341 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2941 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNC2	NM_017637.6 linkuse as main transcript	c.2768C>T	p.Ala923Val	missense_variant	7/7	ENST00000380672.9	NP_060107.3	Q6ZN30-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9 linkuse as main transcript	c.2768C>T	p.Ala923Val	missense_variant	7/7	2	NM_017637.6	ENSP00000370047.3		Q6ZN30-1

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2943

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.00971

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0200

AC:

5022

AN:

250660

Hom.:

AF XY:

0.0205

AC XY:

2776

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0306

AC:

44667

AN:

1461864

Hom.:

814

Cov.:

AF XY:

0.0298

AC XY:

21702

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00439

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00759

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0193

AC:

2941

AN:

152246

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1341

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00544

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00971

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0296

Hom.:

123

Bravo

AF:

0.0190

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0341

AC:

293

ExAC

AF:

0.0209

AC:

2539

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0304

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	BNC2: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 323/13006= 2.4% -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Aug 24, 2015	- -

BNC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypotension

Other:1

not provided, no classification provided

literature only

Centre for molecular medicine, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

0.097

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.073

Sift

Benign

0.12

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.76

P;.

Vest4

0.24

MPC

0.13

ClinPred

0.014

GERP RS

5.5

Varity_R

0.080

gMVP

0.36

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