rs11830202

Positions:

• chr12-1580675-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000339235.4(FBXL14):​c.1194+12198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,024 control chromosomes in the GnomAD database, including 5,216 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 0.19 (5216 hom., cov: 32)
• Consequence: FBXL14 ENST00000339235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

FBXL14 (HGNC:28624): (F-box and leucine rich repeat protein 14) Members of the F-box protein family, such as FBXL14, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

WNT5B (HGNC:16265): (Wnt family member 5B) The WNT gene family consists of structurally related genes which 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 encodes a protein which shows 94% and 80% amino acid identity to the mouse Wnt5b protein and the human WNT5A protein, respectively. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL14	NM_152441.3	c.1194+12198C>T		intron_variant		ENST00000339235.4	NP_689654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL14	ENST00000339235.4	c.1194+12198C>T		intron_variant		1	NM_152441.3	ENSP00000344855	P1
WNT5B	ENST00000537031.5	c.-58+5834G>A		intron_variant		2		ENSP00000439312	P1
WNT5B	ENST00000539198.5	c.-57-50623G>A		intron_variant		4		ENSP00000438414
WNT5B	ENST00000545811.5	c.-58+49725G>A		intron_variant		2		ENSP00000445395

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28493 AN: 151904 Hom.: 5200 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.188 AC: 28556 AN: 152024 Hom.: 5216 Cov.: 32 AF XY: 0.184 AC XY: 13698 AN XY: 74318

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0771

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0944 Hom.: 1354

Bravo AF: 0.207

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.70

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: rs11830202; hg19: chr12-1689841;