chr9-16862282-A-G

Variant names:

• chr9-16862282-A-G
• rs7861573
• NM_017637.6:c.3+8364T>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+8364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,144 control chromosomes in the GnomAD database, including 40,497 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 0.73 (40497 hom., cov: 33)
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	NM_017637.6	MANE Select	c.3+8364T>C		intron	N/A	NP_060107.3
	BNC2	NM_001317940.2		c.-63+8364T>C		intron	N/A	NP_001304869.1
	BNC2	NM_001317939.2		c.3+8364T>C		intron	N/A	NP_001304868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	ENST00000380672.9	TSL:2 MANE Select	c.3+8364T>C		intron	N/A	ENSP00000370047.3	Q6ZN30-1
	BNC2	ENST00000545497.5	TSL:1	c.-394+8364T>C		intron	N/A	ENSP00000444640.2	F5H586
	BNC2	ENST00000613349.4	TSL:1	c.-106+5077T>C		intron	N/A	ENSP00000477717.1	Q06HC7

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110428 AN: 152026 Hom.: 40486 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.726 AC: 110467 AN: 152144 Hom.: 40497 Cov.: 33 AF XY: 0.727 AC XY: 54107 AN XY: 74398

African (AFR) AF: 0.627 AC: 26001 AN: 41484

American (AMR) AF: 0.693 AC: 10605 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4709 AN: 5174

South Asian (SAS) AF: 0.743 AC: 3580 AN: 4820

European-Finnish (FIN) AF: 0.754 AC: 7982 AN: 10588

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52401 AN: 67990

Other (OTH) AF: 0.749 AC: 1585 AN: 2116

Alfa AF: 0.761 Hom.: 141020

Bravo AF: 0.721

Asia WGS AF: 0.773 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.037
DANN	Benign	0.43
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: rs7861573; hg19: chr9-16862280;