7-5480548-ATTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTT

Variant names:

• chr7-5480548-A-AT
• rs1180980635
• NM_024963.6:c.*1226dupA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024963.6(FBXL18):​c.*1226dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00057 (2 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: FBXL18 NM_024963.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL18	NM_024963.6	c.*1226dupA		3_prime_UTR_variant	Exon 5 of 5	ENST00000382368.8	NP_079239.3
FBXL18	NM_001367780.1	c.*1226dupA		3_prime_UTR_variant	Exon 5 of 5		NP_001354709.1
FBXL18	NM_001367781.1	c.*1226dupA		3_prime_UTR_variant	Exon 5 of 5		NP_001354710.1
FBXL18	NM_001363441.2	c.2000+10682dupA		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.*1226dupA		3_prime_UTR_variant	Exon 5 of 5	5	NM_024963.6	ENSP00000371805.3
FBXL18	ENST00000415009.5	n.2000+10682dupA		intron_variant	Intron 4 of 6	2		ENSP00000415064.1

Frequencies

GnomAD3 genomes AF: 0.000570 AC: 23 AN: 40346 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000746

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000539

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000710

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.000570 AC: 23 AN: 40336 Hom.: 2 Cov.: 0 AF XY: 0.000389 AC XY: 7 AN XY: 18014

African (AFR) AF: 0.000480 AC: 5 AN: 10420

American (AMR) AF: 0.000746 AC: 2 AN: 2680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1290

East Asian (EAS) AF: 0.000541 AC: 1 AN: 1848

South Asian (SAS) AF: 0.00 AC: 0 AN: 1162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.000710 AC: 15 AN: 21124

Other (OTH) AF: 0.00 AC: 0 AN: 542

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

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;