9-16789880-C-T

Variant names:

• chr9-16789880-C-T
• rs4961760
• NM_017637.6:c.4-51395G>A

Variant summary

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

The NM_017637.6(BNC2):​c.4-51395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,220 control chromosomes in the GnomAD database, including 58,933 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 0.88 (58933 hom., cov: 33)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 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.4-51395G>A		intron	N/A	NP_060107.3
	BNC2	NM_001317940.2		c.45+42364G>A		intron	N/A	NP_001304869.1
	BNC2	NM_001317939.2		c.4-61883G>A		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.4-51395G>A		intron	N/A	ENSP00000370047.3
	BNC2	ENST00000545497.5	TSL:1	c.-393-61883G>A		intron	N/A	ENSP00000444640.2
	BNC2	ENST00000613349.4	TSL:1	c.-105-61883G>A		intron	N/A	ENSP00000477717.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133604 AN: 152102 Hom.: 58892 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.878 AC: 133703 AN: 152220 Hom.: 58933 Cov.: 33 AF XY: 0.878 AC XY: 65380 AN XY: 74430

African (AFR) AF: 0.787 AC: 32651 AN: 41500

American (AMR) AF: 0.890 AC: 13619 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3176 AN: 3472

East Asian (EAS) AF: 0.877 AC: 4538 AN: 5176

South Asian (SAS) AF: 0.841 AC: 4055 AN: 4820

European-Finnish (FIN) AF: 0.918 AC: 9744 AN: 10618

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62910 AN: 68010

Other (OTH) AF: 0.877 AC: 1856 AN: 2116

Alfa AF: 0.906 Hom.: 163207

Bravo AF: 0.872

Asia WGS AF: 0.841 AC: 2927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.088
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: rs4961760; hg19: chr9-16789878;