17-46850687-G-C

Variant names:

• chr17-46850687-G-C
• rs12602434
• ENST00000575372.5:c.95+17247G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000575372.5(WNT9B):​c.95+17247G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,148 control chromosomes in the GnomAD database, including 3,601 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 0.20 (3601 hom., cov: 32)
• Consequence: WNT9B ENST00000575372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 10 publications found

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:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000575372.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	ENST00000575372.5	TSL:4	c.95+17247G>C		intron	N/A	ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29820 AN: 152030 Hom.: 3594 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.196 AC: 29860 AN: 152148 Hom.: 3601 Cov.: 32 AF XY: 0.201 AC XY: 14974 AN XY: 74370

African (AFR) AF: 0.200 AC: 8289 AN: 41486

American (AMR) AF: 0.280 AC: 4280 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2557 AN: 5170

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1630 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9972 AN: 68018

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.0737 Hom.: 79

Bravo AF: 0.206

Asia WGS AF: 0.476 AC: 1649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.62
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs12602434; hg19: chr17-44928053;