NM_017637.6:c.3+13761C>T

Variant names:

• chr9-16856885-G-A
• rs1416742
• NM_017637.6:c.3+13761C>T

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+13761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,986 control chromosomes in the GnomAD database, including 16,256 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 0.42 (16256 hom., cov: 31)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 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+13761C>T		intron	N/A	NP_060107.3
	BNC2	NM_001317940.2		c.-63+13761C>T		intron	N/A	NP_001304869.1
	BNC2	NM_001317939.2		c.3+13761C>T		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+13761C>T		intron	N/A	ENSP00000370047.3
	BNC2	ENST00000545497.5	TSL:1	c.-394+13761C>T		intron	N/A	ENSP00000444640.2
	BNC2	ENST00000613349.4	TSL:1	c.-106+10474C>T		intron	N/A	ENSP00000477717.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64403 AN: 151866 Hom.: 16258 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.424 AC: 64400 AN: 151986 Hom.: 16256 Cov.: 31 AF XY: 0.418 AC XY: 31032 AN XY: 74272

African (AFR) AF: 0.190 AC: 7884 AN: 41470

American (AMR) AF: 0.364 AC: 5554 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1114 AN: 5160

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4822

European-Finnish (FIN) AF: 0.581 AC: 6131 AN: 10550

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39698 AN: 67940

Other (OTH) AF: 0.422 AC: 888 AN: 2102

Alfa AF: 0.511 Hom.: 9740

Bravo AF: 0.402

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		1.7
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: rs1416742; hg19: chr9-16856883;