3-121625293-A-G

Variant names:

• chr3-121625293-A-G
• rs3772130
• NM_016298.4:c.1915-1402A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016298.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO40	NM_016298.4	MANE Select	c.1915-1402A>G		intron	N/A	NP_057382.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO40	ENST00000338040.6	TSL:1 MANE Select	c.1915-1402A>G		intron	N/A	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

African (AFR) AF: 0.145 AC: 6030 AN: 41520

American (AMR) AF: 0.144 AC: 2210 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3466

East Asian (EAS) AF: 0.0831 AC: 431 AN: 5188

South Asian (SAS) AF: 0.0956 AC: 462 AN: 4832

European-Finnish (FIN) AF: 0.312 AC: 3296 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19389 AN: 67976

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.257 Hom.: 22609

Bravo AF: 0.209

Asia WGS AF: 0.110 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.68
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3772130; hg19: chr3-121344140;