Variant chr12-1593304-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152441.3(FBXL14):c.763C>T(p.Leu255=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00725 in 1,613,370 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 50 hom. )

Consequence

FBXL14
NM_152441.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.79

Variant links:

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]

FBXL14 links:

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]

WNT5B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 12-1593304-G-A is Benign according to our data. Variant chr12-1593304-G-A is described in ClinVar as [Benign]. Clinvar id is 778076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL14	NM_152441.3 linkuse as main transcript	c.763C>T	p.Leu255=	synonymous_variant	1/2	ENST00000339235.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FBXL14	ENST00000339235.4 linkuse as main transcript	c.763C>T	p.Leu255=	synonymous_variant	1/2	1	NM_152441.3	P1
WNT5B	ENST00000537031.5 linkuse as main transcript	c.-58+18463G>A		intron_variant		2		P1
WNT5B	ENST00000539198.5 linkuse as main transcript	c.-57-37994G>A		intron_variant		4
WNT5B	ENST00000545811.5 linkuse as main transcript	c.-57-37994G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

789

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00248

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00895

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00508

AC:

1272

AN:

250458

Hom.:

AF XY:

0.00518

AC XY:

702

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00336

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00931

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00747

AC:

10911

AN:

1460994

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

5277

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00387

Gnomad4 FIN exome

AF:

0.00158

Gnomad4 NFE exome

AF:

0.00911

Gnomad4 OTH exome

AF:

0.00455

GnomAD4 genome

AF:

0.00518

AC:

789

AN:

152376

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

357

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00895

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00479

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00818

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over