chr1-227919220-G-A

Position:

• chr1-227919220-G-A

Variant summary

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

The NM_003395.4(WNT9A):​c.*2298C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,240 control chromosomes in the GnomAD database, including 866 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 0.10 (866 hom., cov: 32)
  • Exomes 𝑓: 0.036 (0 hom.)
• Consequence: WNT9A NM_003395.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

Genes affected

WNT9A (HGNC:12778): (Wnt family member 9A) 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. It is expressed in gastric cancer cell lines. The protein encoded by this gene shows 75% amino acid identity to chicken Wnt14, which has been shown to play a central role in initiating synovial joint formation in the chick limb. This gene is clustered with another family member, WNT3A, in the chromosome 1q42 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9A	NM_003395.4	c.*2298C>T		3_prime_UTR_variant	4/4	ENST00000272164.6	NP_003386.1
WNT9A	XM_011544271.3	c.*2298C>T		3_prime_UTR_variant	4/4		XP_011542573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT9A	ENST00000272164.6	c.*2298C>T		3_prime_UTR_variant	4/4	1	NM_003395.4	ENSP00000272164	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15377 AN: 152094 Hom.: 865 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0991

GnomAD4 exome AF: 0.0357 AC: 1 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.101 AC: 15371 AN: 152212 Hom.: 866 Cov.: 32 AF XY: 0.102 AC XY: 7565 AN XY: 74420

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0729

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.107 Hom.: 1175

Bravo AF: 0.0939

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.96
DANN	Benign	0.81

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: rs12725747; hg19: chr1-228106921; COSMIC: COSV55293879;