rs372193837

Variant names:

• chr17-46872574-G-A
• rs372193837
• NM_003396.3:c.135G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-46872574-G-A
• chr17-46872574-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003396.3(WNT9B):​c.135G>A​(p.Pro45Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,600,106 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P45P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (16 hom.)
• Consequence: WNT9B NM_003396.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.01
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-46872574-G-A is Benign according to our data. Variant chr17-46872574-G-A is described in ClinVar as Benign. ClinVar VariationId is 1632396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.01 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	NM_003396.3	MANE Select	c.135G>A	p.Pro45Pro	synonymous	Exon 2 of 4	NP_003387.1	O14905
	WNT9B	NM_001320458.2		c.135G>A	p.Pro45Pro	synonymous	Exon 2 of 5	NP_001307387.1	E7EPC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	ENST00000290015.7	TSL:1 MANE Select	c.135G>A	p.Pro45Pro	synonymous	Exon 2 of 4	ENSP00000290015.2	O14905
	WNT9B	ENST00000393461.2	TSL:2	c.135G>A	p.Pro45Pro	synonymous	Exon 2 of 5	ENSP00000377105.2	E7EPC3
	WNT9B	ENST00000575372.5	TSL:4	c.153G>A	p.Pro51Pro	synonymous	Exon 2 of 3	ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152232 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00144 AC: 345 AN: 238964 AF XY: 0.00193

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000643 AC: 931 AN: 1447756 Hom.: 16 Cov.: 31 AF XY: 0.000907 AC XY: 652 AN XY: 718590

African (AFR) AF: 0.0000301 AC: 1 AN: 33196

American (AMR) AF: 0.000115 AC: 5 AN: 43610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25336

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39338

South Asian (SAS) AF: 0.0102 AC: 859 AN: 84400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52900

Middle Eastern (MID) AF: 0.000725 AC: 4 AN: 5518

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1103756

Other (OTH) AF: 0.000787 AC: 47 AN: 59702

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152350 Hom.: 1 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74506

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00993 AC: 48 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000484 Hom.: 0

Bravo AF: 0.000102

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.044
DANN	Benign	0.60
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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: rs372193837; hg19: chr17-44949940; COSMIC: COSV51517446;