Variant 7-5500919-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_024963.6(FBXL18):c.1350G>A(p.Lys450Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,567,874 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

FBXL18
NM_024963.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

FBXL18 (HGNC:21874): (F-box and leucine rich repeat protein 18) The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]

FBXL18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-5500919-C-T is Benign according to our data. Variant chr7-5500919-C-T is described in ClinVar as [Benign]. Clinvar id is 726132.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.66 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL18	NM_024963.6 linkuse as main transcript	c.1350G>A	p.Lys450Lys	synonymous_variant	3/5	ENST00000382368.8	NP_079239.3	Q96ME1-4Q96D16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FBXL18	ENST00000382368.8 linkuse as main transcript	c.1350G>A	p.Lys450Lys	synonymous_variant	3/5	5	NM_024963.6	ENSP00000371805.3	Q96ME1-4
FBXL18	ENST00000458142.1 linkuse as main transcript	c.999G>A	p.Lys333Lys	synonymous_variant	1/3	2		ENSP00000405896.1	A0A994ENR3
FBXL18	ENST00000415009.5 linkuse as main transcript	n.1350G>A		non_coding_transcript_exon_variant	3/7	2		ENSP00000415064.1	Q96ME1-2

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000279

AC:

AN:

197166

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

108732

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.000307

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:

0.0000444

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.000146

AC:

206

AN:

1415530

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

699878

show subpopulations

Gnomad4 AFR exome

AF:

0.00452

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.000127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000918

Gnomad4 OTH exome

AF:

0.000532

GnomAD4 genome

AF:

0.000998

AC:

152

AN:

152344

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000292

Hom.:

Bravo

AF:

0.00119

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.4

DANN

Benign

0.57

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