rs2240506

Variant names:

• chr12-1588844-A-G
• rs2240506
• NM_152441.3:c.1194+4029T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152441.3(FBXL14):​c.1194+4029T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,796 control chromosomes in the GnomAD database, including 43,748 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 0.74 (43748 hom., cov: 28)
• Consequence: FBXL14 NM_152441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL14	NM_152441.3	c.1194+4029T>C		intron_variant	Intron 1 of 1	ENST00000339235.4	NP_689654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL14	ENST00000339235.4	c.1194+4029T>C		intron_variant	Intron 1 of 1	1	NM_152441.3	ENSP00000344855.3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112710 AN: 151676 Hom.: 43726 Cov.: 28

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.743 AC: 112775 AN: 151796 Hom.: 43748 Cov.: 28 AF XY: 0.741 AC XY: 54982 AN XY: 74204

African (AFR) AF: 0.536 AC: 22115 AN: 41280

American (AMR) AF: 0.720 AC: 10990 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2945 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2243 AN: 5154

South Asian (SAS) AF: 0.747 AC: 3584 AN: 4798

European-Finnish (FIN) AF: 0.876 AC: 9259 AN: 10564

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 58991 AN: 67960

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.822 Hom.: 95709

Bravo AF: 0.718

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.70
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240506; hg19: chr12-1698010;