17-46850687-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37A2	XM_024450773.2	c.4810-198369G>C		intron_variant	Intron 10 of 10		XP_024306541.1
WNT9B	XM_011525178.3	c.95+17247G>C		intron_variant	Intron 1 of 3		XP_011523480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000575372.5	c.95+17247G>C		intron_variant	Intron 1 of 2	4		ENSP00000458192.1

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.191

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12602434; hg19: chr17-44928053;