9-16851680-T-G

Variant names:

• chr9-16851680-T-G
• rs4961501
• NM_017637.6:c.3+18966A>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+18966A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,018 control chromosomes in the GnomAD database, including 38,868 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 0.71 (38868 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017637.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	NM_017637.6	MANE Select	c.3+18966A>C		intron	N/A	NP_060107.3
	BNC2	NM_001317940.2		c.-63+18966A>C		intron	N/A	NP_001304869.1
	BNC2	NM_001317939.2		c.3+18966A>C		intron	N/A	NP_001304868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	ENST00000380672.9	TSL:2 MANE Select	c.3+18966A>C		intron	N/A	ENSP00000370047.3
	BNC2	ENST00000545497.5	TSL:1	c.-394+18966A>C		intron	N/A	ENSP00000444640.2
	BNC2	ENST00000613349.4	TSL:1	c.-106+15679A>C		intron	N/A	ENSP00000477717.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107231 AN: 151900 Hom.: 38860 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.706 AC: 107275 AN: 152018 Hom.: 38868 Cov.: 32 AF XY: 0.712 AC XY: 52928 AN XY: 74288

African (AFR) AF: 0.530 AC: 21963 AN: 41404

American (AMR) AF: 0.802 AC: 12249 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2531 AN: 3468

East Asian (EAS) AF: 0.902 AC: 4666 AN: 5174

South Asian (SAS) AF: 0.910 AC: 4388 AN: 4820

European-Finnish (FIN) AF: 0.766 AC: 8099 AN: 10568

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51059 AN: 67994

Other (OTH) AF: 0.722 AC: 1522 AN: 2108

Alfa AF: 0.746 Hom.: 53364

Bravo AF: 0.698

Asia WGS AF: 0.896 AC: 3117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.76
PhyloP100		-0.87
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: rs4961501; hg19: chr9-16851678;