chr17-46875165-G-T

Variant names:

• chr17-46875165-G-T
• rs34072914
• NM_003396.3:c.399G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003396.3(WNT9B):​c.399G>T​(p.Arg133Arg) 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, multiple submitters, no conflicts B:2
• 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: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 -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 105 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.399G>T	p.Arg133Arg	synonymous_variant	Exon 3 of 4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.399G>T	p.Arg133Arg	synonymous_variant	Exon 3 of 5		NP_001307387.1
WNT9B	XM_011525178.3	c.417G>T	p.Arg139Arg	synonymous_variant	Exon 3 of 4		XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-173891G>T		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.399G>T	p.Arg133Arg	synonymous_variant	Exon 3 of 4	1	NM_003396.3	ENSP00000290015.2
WNT9B	ENST00000393461.2	c.399G>T	p.Arg133Arg	synonymous_variant	Exon 3 of 5	2		ENSP00000377105.2
WNT9B	ENST00000575372.5	c.*19G>T		downstream_gene_variant		4		ENSP00000458192.1

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

GnomAD2 exomes AF: 0.0273 AC: 6838 AN: 250610 AF XY: 0.0276

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 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 AC: 1674 AN: 33480

Gnomad4 AMR exome AF: 0.0243 AC: 1086 AN: 44722

Gnomad4 ASJ exome AF: 0.0251 AC: 655 AN: 26134

Gnomad4 EAS exome AF: 0.0325 AC: 1290 AN: 39698

Gnomad4 SAS exome AF: 0.0328 AC: 2828 AN: 86248

Gnomad4 FIN exome AF: 0.0104 AC: 553 AN: 53230

Gnomad4 NFE exome AF: 0.0244 AC: 27170 AN: 1112000

Gnomad4 Remaining exome AF: 0.0264 AC: 1597 AN: 60396

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 AC: 0.0487013 AN: 0.0487013

Gnomad4 AMR AF: 0.0292 AC: 0.0292233 AN: 0.0292233

Gnomad4 ASJ AF: 0.0213 AC: 0.0213256 AN: 0.0213256

Gnomad4 EAS AF: 0.0336 AC: 0.0336037 AN: 0.0336037

Gnomad4 SAS AF: 0.0334 AC: 0.0333886 AN: 0.0333886

Gnomad4 FIN AF: 0.00941 AC: 0.00941088 AN: 0.00941088

Gnomad4 NFE AF: 0.0279 AC: 0.0279444 AN: 0.0279444

Gnomad4 OTH AF: 0.0307 AC: 0.0307183 AN: 0.0307183

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.64
Mutation Taster		=97/3	polymorphism (auto)

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;