9-16733959-A-G

Variant names:

• chr9-16733959-A-G
• rs2840290
• NM_017637.6:c.129+4401T>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.129+4401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,920 control chromosomes in the GnomAD database, including 20,076 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 0.47 (20076 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.129+4401T>C		intron_variant	Intron 2 of 6	ENST00000380672.9	NP_060107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9	c.129+4401T>C		intron_variant	Intron 2 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70706 AN: 151804 Hom.: 20020 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.466 AC: 70826 AN: 151920 Hom.: 20076 Cov.: 32 AF XY: 0.470 AC XY: 34912 AN XY: 74232

African (AFR) AF: 0.740 AC: 30661 AN: 41456

American (AMR) AF: 0.542 AC: 8271 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1287 AN: 3464

East Asian (EAS) AF: 0.890 AC: 4600 AN: 5166

South Asian (SAS) AF: 0.569 AC: 2738 AN: 4812

European-Finnish (FIN) AF: 0.259 AC: 2726 AN: 10514

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19188 AN: 67928

Other (OTH) AF: 0.443 AC: 935 AN: 2112

Alfa AF: 0.333 Hom.: 4297

Bravo AF: 0.499

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.051
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: rs2840290; hg19: chr9-16733957;