rs34072914

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
• Publications: 9 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 -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 VariationId 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 passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 105 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003396.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	NM_003396.3	MANE Select	c.399G>T	p.Arg133Arg	synonymous	Exon 3 of 4	NP_003387.1
	WNT9B	NM_001320458.2		c.399G>T	p.Arg133Arg	synonymous	Exon 3 of 5	NP_001307387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	ENST00000290015.7	TSL:1 MANE Select	c.399G>T	p.Arg133Arg	synonymous	Exon 3 of 4	ENSP00000290015.2
	WNT9B	ENST00000393461.2	TSL:2	c.399G>T	p.Arg133Arg	synonymous	Exon 3 of 5	ENSP00000377105.2
	WNT9B	ENST00000575372.5	TSL:4	c.*19G>T		downstream_gene	N/A	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

African (AFR) AF: 0.0500 AC: 1674 AN: 33480

American (AMR) AF: 0.0243 AC: 1086 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 655 AN: 26134

East Asian (EAS) AF: 0.0325 AC: 1290 AN: 39698

South Asian (SAS) AF: 0.0328 AC: 2828 AN: 86248

European-Finnish (FIN) AF: 0.0104 AC: 553 AN: 53230

Middle Eastern (MID) AF: 0.0355 AC: 205 AN: 5768

European-Non Finnish (NFE) AF: 0.0244 AC: 27170 AN: 1112000

Other (OTH) 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

African (AFR) AF: 0.0487 AC: 2025 AN: 41580

American (AMR) AF: 0.0292 AC: 447 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5178

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4822

European-Finnish (FIN) AF: 0.00941 AC: 100 AN: 10626

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1901 AN: 68028

Other (OTH) AF: 0.0307 AC: 65 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.98
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

Other links and lift over

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