NM_017637.6:c.669+39780T>C

Variant names:

• chr9-16512750-A-G
• rs10124550
• NM_017637.6:c.669+39780T>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.669+39780T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,222 control chromosomes in the GnomAD database, including 1,250 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 0.11 (1250 hom., cov: 32)
• Consequence: BNC2 NM_017637.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860
• Publications: 4 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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6	c.669+39780T>C		intron_variant	Intron 5 of 6	ENST00000380672.9	NP_060107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9	c.669+39780T>C		intron_variant	Intron 5 of 6	2	NM_017637.6	ENSP00000370047.3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16867 AN: 152104 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.111 AC: 16909 AN: 152222 Hom.: 1250 Cov.: 32 AF XY: 0.115 AC XY: 8548 AN XY: 74420

African (AFR) AF: 0.167 AC: 6933 AN: 41518

American (AMR) AF: 0.123 AC: 1886 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1504 AN: 5170

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4816

European-Finnish (FIN) AF: 0.107 AC: 1129 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3895 AN: 68034

Other (OTH) AF: 0.109 AC: 230 AN: 2116

Alfa AF: 0.0850 Hom.: 776

Bravo AF: 0.117

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.5
DANN	Benign	0.80
PhyloP100		0.86
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: rs10124550; hg19: chr9-16512748;