chr7-5480548-ATTTTTTTTTTTT-A

Variant names:

• chr7-5480548-ATTTTTTTTTTTT-A
• rs1180980635
• NM_024963.6:c.*1215_*1226delAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024963.6(FBXL18):​c.*1215_*1226delAAAAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (4 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: FBXL18 NM_024963.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL18	NM_024963.6	c.*1215_*1226delAAAAAAAAAAAA		3_prime_UTR_variant	Exon 5 of 5	ENST00000382368.8	NP_079239.3
FBXL18	NM_001367780.1	c.*1215_*1226delAAAAAAAAAAAA		3_prime_UTR_variant	Exon 5 of 5		NP_001354709.1
FBXL18	NM_001367781.1	c.*1215_*1226delAAAAAAAAAAAA		3_prime_UTR_variant	Exon 5 of 5		NP_001354710.1
FBXL18	NM_001363441.2	c.2000+10671_2000+10682delAAAAAAAAAAAA		intron_variant	Intron 4 of 4		NP_001350370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL18	ENST00000382368.8	c.*1215_*1226delAAAAAAAAAAAA		3_prime_UTR_variant	Exon 5 of 5	5	NM_024963.6	ENSP00000371805.3
FBXL18	ENST00000415009.5	n.2000+10671_2000+10682delAAAAAAAAAAAA		intron_variant	Intron 4 of 6	2		ENSP00000415064.1

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 915 AN: 39716 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00355

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0170

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0229 AC: 910 AN: 39704 Hom.: 4 Cov.: 0 AF XY: 0.0267 AC XY: 473 AN XY: 17722

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0367 AC: 371 AN: 10116

American (AMR) AF: 0.0222 AC: 59 AN: 2654

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 3 AN: 1290

East Asian (EAS) AF: 0.0635 AC: 114 AN: 1794

South Asian (SAS) AF: 0.0353 AC: 40 AN: 1132

European-Finnish (FIN) AF: 0.0536 AC: 49 AN: 914

Middle Eastern (MID) AF: 0.0323 AC: 2 AN: 62

European-Non Finnish (NFE) AF: 0.0125 AC: 262 AN: 20926

Other (OTH) AF: 0.0169 AC: 9 AN: 534

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1180980635; hg19: chr7-5520179;