rs10216189

Positions:

• chr7-5485174-G-A

Variant summary

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

The NM_024963.6(FBXL18):​c.2001-3243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,932 control chromosomes in the GnomAD database, including 17,950 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 0.48 (17950 hom., cov: 31)
• Consequence: FBXL18 NM_024963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL18	NM_024963.6	c.2001-3243C>T		intron_variant		ENST00000382368.8	NP_079239.3
FBXL18	NM_001363441.2	c.2000+6057C>T		intron_variant			NP_001350370.1
FBXL18	NM_001367780.1	c.1701-3243C>T		intron_variant			NP_001354709.1
FBXL18	NM_001367781.1	c.1701-3243C>T		intron_variant			NP_001354710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL18	ENST00000382368.8	c.2001-3243C>T		intron_variant		5	NM_024963.6	ENSP00000371805	P1
FBXL18	ENST00000415009.5	c.2000+6057C>T		intron_variant, NMD_transcript_variant		2		ENSP00000415064

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73302 AN: 151814 Hom.: 17936 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.483 AC: 73352 AN: 151932 Hom.: 17950 Cov.: 31 AF XY: 0.483 AC XY: 35842 AN XY: 74258

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.469

Alfa AF: 0.470 Hom.: 15701

Bravo AF: 0.477

Asia WGS AF: 0.538 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.76

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: rs10216189; hg19: chr7-5524805;