rs4968282

Positions:

• chr17-46881571-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320458.2(WNT9B):​c.905-3463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,832 control chromosomes in the GnomAD database, including 7,186 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 0.31 (7186 hom., cov: 32)
• Consequence: WNT9B NM_001320458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

Genes affected

WNT9B (HGNC:12779): (Wnt family member 9B) The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. Study of its expression in the teratocarcinoma cell line NT2 suggests that it may be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid. This gene is clustered with WNT3, another family member, in the chromosome 17q21 region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

LRRC37A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_001320458.2	c.905-3463A>G		intron_variant
LRRC37A2	XM_024450773.2	c.4810-167485A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000393461.2	c.905-3463A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46315 AN: 151712 Hom.: 7174 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.305 AC: 46353 AN: 151832 Hom.: 7186 Cov.: 32 AF XY: 0.307 AC XY: 22785 AN XY: 74208

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.318

Alfa AF: 0.293 Hom.: 13576

Bravo AF: 0.310

Asia WGS AF: 0.309 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4968282; hg19: chr17-44958937;