rs117452684

Variant names:

• chr9-16419521-G-A
• rs117452684
• NM_017637.6:c.2768C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-16419521-G-A
• chr9-16419521-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017637.6(BNC2):​c.2768C>T​(p.Ala923Val) variant causes a missense change. The variant allele was found at a frequency of 0.0295 in 1,614,110 control chromosomes in the GnomAD database, including 848 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A923G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.019 (34 hom., cov: 31)
  • Exomes 𝑓: 0.031 (814 hom.)
• Consequence: BNC2 NM_017637.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: 4.83
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• posterior urethral valve

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004229605).
• BP6: Variant 9-16419521-G-A is Benign according to our data. Variant chr9-16419521-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 120238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0193 (2941/152246) while in subpopulation NFE AF = 0.0323 (2199/68012). AF 95% confidence interval is 0.0312. There are 34 homozygotes in GnomAd4. There are 1341 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	NM_017637.6	MANE Select	c.2768C>T	p.Ala923Val	missense	Exon 7 of 7	NP_060107.3
	BNC2	NM_001317940.2		c.2483C>T	p.Ala828Val	missense	Exon 6 of 6	NP_001304869.1
	BNC2	NM_001317939.2		c.*112C>T		3_prime_UTR	Exon 7 of 7	NP_001304868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNC2	ENST00000380672.9	TSL:2 MANE Select	c.2768C>T	p.Ala923Val	missense	Exon 7 of 7	ENSP00000370047.3	Q6ZN30-1
	BNC2	ENST00000545497.5	TSL:1	c.*112C>T		3_prime_UTR	Exon 7 of 7	ENSP00000444640.2	F5H586
	BNC2	ENST00000411752.5	TSL:1	c.*144C>T		3_prime_UTR	Exon 5 of 5	ENSP00000392212.1	H0Y4J1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2943 AN: 152128 Hom.: 34 Cov.: 31

Gnomad AFR AF: 0.00545

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00971

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.0200 AC: 5022 AN: 250660 AF XY: 0.0205

Gnomad AFR exome AF: 0.00523

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.0333

Gnomad OTH exome AF: 0.0189

GnomAD4 exome AF: 0.0306 AC: 44667 AN: 1461864 Hom.: 814 Cov.: 35 AF XY: 0.0298 AC XY: 21702 AN XY: 727234

African (AFR) AF: 0.00439 AC: 147 AN: 33480

American (AMR) AF: 0.0112 AC: 500 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0220 AC: 574 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00759 AC: 655 AN: 86258

European-Finnish (FIN) AF: 0.0123 AC: 655 AN: 53418

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.0364 AC: 40507 AN: 1111984

Other (OTH) AF: 0.0264 AC: 1592 AN: 60396

GnomAD4 genome AF: 0.0193 AC: 2941 AN: 152246 Hom.: 34 Cov.: 31 AF XY: 0.0180 AC XY: 1341 AN XY: 74440

African (AFR) AF: 0.00544 AC: 226 AN: 41570

American (AMR) AF: 0.0165 AC: 253 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.00971 AC: 103 AN: 10604

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0323 AC: 2199 AN: 68012

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0290 Hom.: 238

Bravo AF: 0.0190

TwinsUK AF: 0.0353 AC: 131

ALSPAC AF: 0.0381 AC: 147

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.0341 AC: 293

ExAC AF: 0.0209 AC: 2539

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.0303

EpiControl AF: 0.0304

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	BNC2-related disorder (1)
-	-	-	Hypotension (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Benign	0.097
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.073
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.76	P
Vest4		0.24
MPC		0.13
ClinPred		0.014	T
GERP RS		5.5
Varity_R		0.080
gMVP		0.36
Mutation Taster		=96/4	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: rs117452684; hg19: chr9-16419519;