17-46875142-G-A

Position:

• chr17-46875142-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000290015.7(WNT9B):​c.376G>A​(p.Ala126Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,906 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (10 hom.)
• Consequence: WNT9B ENST00000290015.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.00

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016923219).
• BP6: Variant 17-46875142-G-A is Benign according to our data. Variant chr17-46875142-G-A is described in ClinVar as [Benign]. Clinvar id is 2124886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00695 (1059/152266) while in subpopulation AFR AF= 0.0239 (993/41526). AF 95% confidence interval is 0.0227. There are 15 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.376G>A	p.Ala126Thr	missense_variant	3/4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.376G>A	p.Ala126Thr	missense_variant	3/5		NP_001307387.1
WNT9B	XM_011525178.3	c.394G>A	p.Ala132Thr	missense_variant	3/4		XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-173914G>A		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.376G>A	p.Ala126Thr	missense_variant	3/4	1	NM_003396.3	ENSP00000290015	P1
WNT9B	ENST00000393461.2	c.376G>A	p.Ala126Thr	missense_variant	3/5	2		ENSP00000377105
WNT9B	ENST00000575372.5	c.394G>A	p.Ala132Thr	missense_variant	3/3	4		ENSP00000458192

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1060 AN: 152148 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00178 AC: 446 AN: 250234 Hom.: 7 AF XY: 0.00133 AC XY: 180 AN XY: 135554

Gnomad AFR exome AF: 0.0252

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000716 AC: 1046 AN: 1461640 Hom.: 10 Cov.: 31 AF XY: 0.000601 AC XY: 437 AN XY: 727146

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00695 AC: 1059 AN: 152266 Hom.: 15 Cov.: 33 AF XY: 0.00663 AC XY: 494 AN XY: 74458

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00108 Hom.: 2

Bravo AF: 0.00775

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00219 AC: 266

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	.;D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	.;N;N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.99, 1.0	.;D;D
Vest4		0.75, 0.74
MVP		0.91
MPC		0.79
ClinPred		0.058	T
GERP RS		4.6
Varity_R		0.46
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116126279; hg19: chr17-44952508;