17-46871734-G-C

Variant names:

• chr17-46871734-G-C
• rs11079740
• NM_003396.3:c.78-783G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003396.3(WNT9B):​c.78-783G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,136 control chromosomes in the GnomAD database, including 1,456 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1456 hom., cov: 32)
• Consequence: WNT9B NM_003396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

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.78-783G>C		intron	N/A	NP_003387.1
	WNT9B	NM_001320458.2		c.78-783G>C		intron	N/A	NP_001307387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	ENST00000290015.7	TSL:1 MANE Select	c.78-783G>C		intron	N/A	ENSP00000290015.2
	WNT9B	ENST00000393461.2	TSL:2	c.78-783G>C		intron	N/A	ENSP00000377105.2
	WNT9B	ENST00000575372.5	TSL:4	c.96-783G>C		intron	N/A	ENSP00000458192.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20345 AN: 152018 Hom.: 1459 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20352 AN: 152136 Hom.: 1456 Cov.: 32 AF XY: 0.139 AC XY: 10323 AN XY: 74378

African (AFR) AF: 0.130 AC: 5404 AN: 41500

American (AMR) AF: 0.140 AC: 2141 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1541 AN: 5174

South Asian (SAS) AF: 0.130 AC: 625 AN: 4812

European-Finnish (FIN) AF: 0.206 AC: 2179 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7708 AN: 67992

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.0765 Hom.: 104

Bravo AF: 0.135

Asia WGS AF: 0.185 AC: 642 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.53
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs11079740; hg19: chr17-44949100;