17-46872579-A-G

Position:

• chr17-46872579-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000290015.7(WNT9B):​c.140A>G​(p.Gln47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 1,602,258 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (75 hom.)
• Consequence: WNT9B ENST00000290015.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005423963).
• BP6: Variant 17-46872579-A-G is Benign according to our data. Variant chr17-46872579-A-G is described in ClinVar as [Benign]. Clinvar id is 1598579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.140A>G	p.Gln47Arg	missense_variant	2/4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.140A>G	p.Gln47Arg	missense_variant	2/5		NP_001307387.1
WNT9B	XM_011525178.3	c.158A>G	p.Gln53Arg	missense_variant	2/4		XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-176477A>G		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.140A>G	p.Gln47Arg	missense_variant	2/4	1	NM_003396.3	ENSP00000290015	P1
WNT9B	ENST00000393461.2	c.140A>G	p.Gln47Arg	missense_variant	2/5	2		ENSP00000377105
WNT9B	ENST00000575372.5	c.158A>G	p.Gln53Arg	missense_variant	2/3	4		ENSP00000458192

Frequencies

GnomAD3 genomes AF: 0.00544 AC: 828 AN: 152224 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00741 AC: 1785 AN: 240810 Hom.: 23 AF XY: 0.00796 AC XY: 1042 AN XY: 130832

Gnomad AFR exome AF: 0.000582

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00235

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0136

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.00639

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00649 AC: 9405 AN: 1449916 Hom.: 75 Cov.: 31 AF XY: 0.00665 AC XY: 4790 AN XY: 720068

Gnomad4 AFR exome AF: 0.000452

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00169

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.00594

Gnomad4 OTH exome AF: 0.00594

GnomAD4 genome AF: 0.00544 AC: 828 AN: 152342 Hom.: 4 Cov.: 32 AF XY: 0.00615 AC XY: 458 AN XY: 74502

Gnomad4 AFR AF: 0.000986

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.00650

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00510 Hom.: 1

Bravo AF: 0.00337

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00605 AC: 52

ExAC AF: 0.00702 AC: 851

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.27	.;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.79	D
MetaRNN	Benign	0.0054	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	.;L;.
MutationTaster	Benign	0.86	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.69	.;N;N
REVEL	Benign	0.13
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.072, 0.039	.;B;B
Vest4		0.14, 0.15
MVP		0.90
MPC		0.30
ClinPred		0.0094	T
GERP RS		4.5
Varity_R		0.066
gMVP		0.50

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: rs118185468; hg19: chr17-44949945;