rs2165846

Positions:

• chr17-46864000-A-G
• chr17-46864000-A-T

Variant summary

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

The NM_003396.3(WNT9B):​c.78-8517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,056 control chromosomes in the GnomAD database, including 21,075 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 0.51 (21075 hom., cov: 32)
• Consequence: WNT9B NM_003396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_003396.3	c.78-8517A>G		intron_variant		ENST00000290015.7
WNT9B	NM_001320458.2	c.78-8517A>G		intron_variant
WNT9B	XM_011525178.3	c.96-8517A>G		intron_variant
LRRC37A2	XM_024450773.2	c.4810-185056A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000290015.7	c.78-8517A>G		intron_variant		1	NM_003396.3	P1
WNT9B	ENST00000393461.2	c.78-8517A>G		intron_variant		2
WNT9B	ENST00000575372.5	c.96-8517A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77360 AN: 151938 Hom.: 21043 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.509 AC: 77435 AN: 152056 Hom.: 21075 Cov.: 32 AF XY: 0.516 AC XY: 38324 AN XY: 74320

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.483

Alfa AF: 0.418 Hom.: 20359

Bravo AF: 0.524

Asia WGS AF: 0.733 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.3
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs2165846; hg19: chr17-44941366;