9-16848792-C-T

Variant names:

• chr9-16848792-C-T
• rs1339552
• NM_017637.6:c.3+21854G>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.3+21854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,978 control chromosomes in the GnomAD database, including 21,939 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 0.52 (21939 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.3+21854G>A		intron_variant	Intron 1 of 6	ENST00000380672.9	NP_060107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9	c.3+21854G>A		intron_variant	Intron 1 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79118 AN: 151860 Hom.: 21902 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.521 AC: 79211 AN: 151978 Hom.: 21939 Cov.: 32 AF XY: 0.530 AC XY: 39367 AN XY: 74296

African (AFR) AF: 0.624 AC: 25855 AN: 41432

American (AMR) AF: 0.614 AC: 9388 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1837 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4062 AN: 5174

South Asian (SAS) AF: 0.787 AC: 3794 AN: 4818

European-Finnish (FIN) AF: 0.419 AC: 4419 AN: 10536

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28021 AN: 67950

Other (OTH) AF: 0.534 AC: 1129 AN: 2114

Alfa AF: 0.459 Hom.: 13727

Bravo AF: 0.536

Asia WGS AF: 0.781 AC: 2714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.35
PhyloP100		-1.2
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: rs1339552; hg19: chr9-16848790; COSMIC: COSV66143410;