17-46875165-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_003396.3(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 NM_003396.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.982

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 -15 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_single_submitter, 1 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 GnomAd at 103 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_003396.3	c.399G>T	p.Arg133=	synonymous_variant	3/4	ENST00000290015.7
WNT9B	NM_001320458.2	c.399G>T	p.Arg133=	synonymous_variant	3/5
WNT9B	XM_011525178.3	c.417G>T	p.Arg139=	synonymous_variant	3/4
LRRC37A2	XM_024450773.2	c.4810-173891G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000290015.7	c.399G>T	p.Arg133=	synonymous_variant	3/4	1	NM_003396.3	P1
WNT9B	ENST00000393461.2	c.399G>T	p.Arg133=	synonymous_variant	3/5	2
WNT9B	ENST00000575372.5			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5002 AN: 152202 Hom.: 103 Cov.: 33

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

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.: 31 AF XY: 0.0258 AC XY: 18782 AN XY: 727162

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.: 33 AF XY: 0.0312 AC XY: 2326 AN XY: 74476

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.: 39

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs34072914; hg19: chr17-44952531; COSMIC: COSV51518549; COSMIC: COSV51518549;