rs1712

Variant names:

• chr6-152970730-C-T
• rs1712
• NM_012177.5:c.*433G>A

Variant summary

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

The NM_012177.5(FBXO5):​c.*433G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,700 control chromosomes in the GnomAD database, including 3,496 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 0.21 (3488 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8 hom.)
• Consequence: FBXO5 NM_012177.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638

Genes affected

FBXO5 (HGNC:13584): (F-box protein 5) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO5	NM_012177.5	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000229758.8	NP_036309.1
FBXO5	NM_001142522.3	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001135994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO5	ENST00000229758	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_012177.5	ENSP00000229758.3
FBXO5	ENST00000367241	c.*433G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000356210.3
FBXO5	ENST00000477822.2	n.2399G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31341 AN: 151852 Hom.: 3477 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.124 AC: 91 AN: 732 Hom.: 8 Cov.: 0 AF XY: 0.148 AC XY: 56 AN XY: 378

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.207 AC: 31397 AN: 151968 Hom.: 3488 Cov.: 32 AF XY: 0.208 AC XY: 15492 AN XY: 74302

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.171

Alfa AF: 0.196 Hom.: 844

Bravo AF: 0.213

Asia WGS AF: 0.212 AC: 733 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.5
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1712; hg19: chr6-153291865;