rs12379183

Variant names:

• chr9-16865701-A-G
• rs12379183
• NM_017637.6:c.3+4945T>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.3+4945T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,058 control chromosomes in the GnomAD database, including 5,193 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 0.26 (5193 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.3+4945T>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.3+4945T>C		intron_variant	Intron 1 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39028 AN: 151940 Hom.: 5172 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.257 AC: 39092 AN: 152058 Hom.: 5193 Cov.: 32 AF XY: 0.256 AC XY: 19032 AN XY: 74296

African (AFR) AF: 0.310 AC: 12869 AN: 41488

American (AMR) AF: 0.296 AC: 4526 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3470

East Asian (EAS) AF: 0.0940 AC: 488 AN: 5192

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2605 AN: 10562

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15725 AN: 67934

Other (OTH) AF: 0.246 AC: 519 AN: 2114

Alfa AF: 0.236 Hom.: 3373

Bravo AF: 0.259

Asia WGS AF: 0.228 AC: 790 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.37
PhyloP100		-0.49
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: rs12379183; hg19: chr9-16865699; COSMIC: COSV66143448;