chr9-16801852-A-C

Variant names:

• chr9-16801852-A-C
• rs2254193
• NM_017637.6:c.4-63367T>G

Variant summary

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

The NM_017637.6(BNC2):​c.4-63367T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,068 control chromosomes in the GnomAD database, including 579 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 0.084 (579 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.4-63367T>G		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.4-63367T>G		intron_variant	Intron 1 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12777 AN: 151952 Hom.: 580 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.00792

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0841 AC: 12786 AN: 152068 Hom.: 579 Cov.: 32 AF XY: 0.0842 AC XY: 6257 AN XY: 74350

African (AFR) AF: 0.110 AC: 4558 AN: 41466

American (AMR) AF: 0.0981 AC: 1499 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 335 AN: 3468

East Asian (EAS) AF: 0.00793 AC: 41 AN: 5168

South Asian (SAS) AF: 0.125 AC: 599 AN: 4804

European-Finnish (FIN) AF: 0.0744 AC: 786 AN: 10570

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4737 AN: 67998

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0775 Hom.: 408

Bravo AF: 0.0858

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		0.20
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: rs2254193; hg19: chr9-16801850;