rs1530364

Positions:

• chr17-46874411-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003396.3(WNT9B):​c.335-690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,042 control chromosomes in the GnomAD database, including 6,770 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 0.30 (6770 hom., cov: 32)
• Consequence: WNT9B NM_003396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_003396.3	c.335-690G>A		intron_variant		ENST00000290015.7
WNT9B	NM_001320458.2	c.335-690G>A		intron_variant
WNT9B	XM_011525178.3	c.353-690G>A		intron_variant
LRRC37A2	XM_024450773.2	c.4810-174645G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000290015.7	c.335-690G>A		intron_variant		1	NM_003396.3	P1
WNT9B	ENST00000393461.2	c.335-690G>A		intron_variant		2
WNT9B	ENST00000575372.5	c.353-690G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44895 AN: 151924 Hom.: 6759 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.295 AC: 44927 AN: 152042 Hom.: 6770 Cov.: 32 AF XY: 0.298 AC XY: 22148 AN XY: 74320

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.310

Alfa AF: 0.295 Hom.: 3897

Bravo AF: 0.296

Asia WGS AF: 0.303 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1530364; hg19: chr17-44951777;