Variant 17-46875165-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000290015.7(WNT9B):c.399G>T(p.Arg133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,613,996 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 105 hom., cov: 33)

Exomes 𝑓: 0.025 ( 550 hom. )

Consequence

WNT9B
ENST00000290015.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.982

Variant links:

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]

WNT9B links:

LRRC37A2 (HGNC:):

LRRC37A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 17-46875165-G-T is Benign according to our data. Variant chr17-46875165-G-T is described in ClinVar as [Benign]. Clinvar id is 1578578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.982 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.033 (5019/152320) while in subpopulation AFR AF= 0.0487 (2025/41580). AF 95% confidence interval is 0.0469. There are 105 homozygotes in gnomad4. There are 2326 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 105 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WNT9B	NM_003396.3 linkuse as main transcript	c.399G>T	p.Arg133=	synonymous_variant	3/4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2 linkuse as main transcript	c.399G>T	p.Arg133=	synonymous_variant	3/5		NP_001307387.1
WNT9B	XM_011525178.3 linkuse as main transcript	c.417G>T	p.Arg139=	synonymous_variant	3/4		XP_011523480.1
LRRC37A2	XM_024450773.2 linkuse as main transcript	c.4810-173891G>T		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WNT9B	ENST00000290015.7 linkuse as main transcript	c.399G>T	p.Arg133=	synonymous_variant	3/4	1	NM_003396.3	ENSP00000290015	P1
WNT9B	ENST00000393461.2 linkuse as main transcript	c.399G>T	p.Arg133=	synonymous_variant	3/5	2		ENSP00000377105
WNT9B	ENST00000575372.5 linkuse as main transcript			downstream_gene_variant		4		ENSP00000458192

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5002

AN:

152202

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0335

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.00941

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0273

AC:

6838

AN:

250610

Hom.:

117

AF XY:

0.0276

AC XY:

3749

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.0246

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.0327

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.0260

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0254

AC:

37058

AN:

1461676

Hom.:

550

Cov.:

AF XY:

0.0258

AC XY:

18782

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0500

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0325

Gnomad4 SAS exome

AF:

0.0328

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0330

AC:

5019

AN:

152320

Hom.:

105

Cov.:

AF XY:

0.0312

AC XY:

2326

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0487

Gnomad4 AMR

AF:

0.0292

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.0334

Gnomad4 FIN

AF:

0.00941

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.0295

EpiControl

AF:

0.0274

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over