9-16804084-A-G

Variant names:

• chr9-16804084-A-G
• rs7861010
• NM_017637.6:c.4-65599T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017637.6(BNC2):​c.4-65599T>C variant causes a intron change. The variant allele was found at a frequency of 0.265 in 152,206 control chromosomes in the GnomAD database, including 8,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (8733 hom., cov: 33)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• lower urinary tract obstruction, congenital

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• posterior urethral valve

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.4-65599T>C		intron_variant	Intron 1 of 6	ENST00000380672.9	NP_060107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9	c.4-65599T>C		intron_variant	Intron 1 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40322 AN: 152088 Hom.: 8717 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40385 AN: 152206 Hom.: 8733 Cov.: 33 AF XY: 0.268 AC XY: 19942 AN XY: 74418

African (AFR) AF: 0.536 AC: 22248 AN: 41498

American (AMR) AF: 0.253 AC: 3864 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3618 AN: 5176

South Asian (SAS) AF: 0.402 AC: 1939 AN: 4818

European-Finnish (FIN) AF: 0.0855 AC: 907 AN: 10610

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.0933 AC: 6349 AN: 68018

Other (OTH) AF: 0.277 AC: 585 AN: 2114

Alfa AF: 0.133 Hom.: 1893

Bravo AF: 0.294

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.55
PhyloP100		4.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7861010; hg19: chr9-16804082;