Variant 9-16419369-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017637.6(BNC2):c.2920A>G(p.Ile974Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,606,930 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 13 hom., cov: 31)

Exomes 𝑓: 0.013 ( 164 hom. )

Consequence

BNC2
NM_017637.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 2.04

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048466623).

BP6

Variant 9-16419369-T-C is Benign according to our data. Variant chr9-16419369-T-C is described in ClinVar as [Benign]. Clinvar id is 120240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00898 (1368/152270) while in subpopulation NFE AF= 0.016 (1090/68008). AF 95% confidence interval is 0.0152. There are 13 homozygotes in gnomad4. There are 632 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1368 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNC2	NM_017637.6 link	c.2920A>G	p.Ile974Val	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 link	c.2920A>G	p.Ile974Val	missense_variant	7/7	2	NM_017637.6	ENSP00000370047.3		Q6ZN30-1

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1368

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00878

AC:

2158

AN:

245898

Hom.:

AF XY:

0.00863

AC XY:

1145

AN XY:

132654

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.00649

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.00952

GnomAD4 exome

AF:

0.0131

AC:

19096

AN:

1454660

Hom.:

164

Cov.:

AF XY:

0.0127

AC XY:

9206

AN XY:

722756

show subpopulations

Gnomad4 AFR exome

AF:

0.00208

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.00821

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.00855

GnomAD4 genome

AF:

0.00898

AC:

1368

AN:

152270

Hom.:

Cov.:

AF XY:

0.00849

AC XY:

632

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00277

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.00880

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0156

AC:

134

ExAC

AF:

0.00911

AC:

1106

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.039

Sift

Benign

1.0

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0090

B;.

Vest4

0.11

MVP

0.043

MPC

0.11

ClinPred

0.0040

GERP RS

4.8

Varity_R

0.030

gMVP

0.28

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