rs2165846

Variant names:

• chr17-46864000-A-G
• rs2165846
• NM_003396.3:c.78-8517A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=-0.62).
• 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 rank	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.78-8517A>G		intron_variant	Intron 1 of 3	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.78-8517A>G		intron_variant	Intron 1 of 4		NP_001307387.1
LRRC37A2	XM_024450773.2	c.4810-185056A>G		intron_variant	Intron 10 of 10		XP_024306541.1
WNT9B	XM_011525178.3	c.96-8517A>G		intron_variant	Intron 1 of 3		XP_011523480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.78-8517A>G		intron_variant	Intron 1 of 3	1	NM_003396.3	ENSP00000290015.2
WNT9B	ENST00000393461.2	c.78-8517A>G		intron_variant	Intron 1 of 4	2		ENSP00000377105.2
WNT9B	ENST00000575372.5	c.96-8517A>G		intron_variant	Intron 1 of 2	4		ENSP00000458192.1

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

African (AFR) AF: 0.639 AC: 26489 AN: 41460

American (AMR) AF: 0.549 AC: 8392 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4569 AN: 5174

South Asian (SAS) AF: 0.584 AC: 2820 AN: 4828

European-Finnish (FIN) AF: 0.477 AC: 5053 AN: 10588

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26797 AN: 67924

Other (OTH) AF: 0.483 AC: 1020 AN: 2110

Alfa AF: 0.429 Hom.: 26720

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
PhyloP100		-0.43
Mutation Taster		=100/0	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: rs2165846; hg19: chr17-44941366;