Variant 9-16419272-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017637.6(BNC2):c.3017C>T(p.Ala1006Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

BNC2
NM_017637.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.14

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003689289).

BP6

Variant 9-16419272-G-A is Benign according to our data. Variant chr9-16419272-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2077000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNC2	NM_017637.6 linkuse as main transcript	c.3017C>T	p.Ala1006Val	missense_variant	7/7	ENST00000380672.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNC2	ENST00000380672.9 linkuse as main transcript	c.3017C>T	p.Ala1006Val	missense_variant	7/7	2	NM_017637.6	P2	Q6ZN30-1

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000271

AC:

AN:

250836

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.0000869

AC:

127

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152330

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.00112

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 08, 2023

- -

BNC2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2023

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.020

Sift

Benign

0.18

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

B;.

Vest4

0.017

MVP

0.068

MPC

0.13

ClinPred

0.0087

GERP RS

4.2

Varity_R

0.027

gMVP

0.31

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

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