rs3772130

Positions:

• chr3-121625293-A-G

Variant summary

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

The NM_016298.4(FBXO40):​c.1915-1402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,158 control chromosomes in the GnomAD database, including 4,207 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 0.22 (4207 hom., cov: 32)
• Consequence: FBXO40 NM_016298.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

Genes affected

FBXO40 (HGNC:29816): (F-box protein 40) Members of the F-box protein family, such as FBXO40, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO40	NM_016298.4	c.1915-1402A>G		intron_variant		ENST00000338040.6	NP_057382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO40	ENST00000338040.6	c.1915-1402A>G		intron_variant		1	NM_016298.4	ENSP00000337510.4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33367 AN: 152040 Hom.: 4208 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.219 AC: 33361 AN: 152158 Hom.: 4207 Cov.: 32 AF XY: 0.213 AC XY: 15852 AN XY: 74386

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0831

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.208

Alfa AF: 0.262 Hom.: 11291

Bravo AF: 0.209

Asia WGS AF: 0.110 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.68

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: rs3772130; hg19: chr3-121344140;