rs725310

Variant names:

• chr3-48377081-C-T
• rs725310
• NM_207102.2:c.406-1236C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207102.2(FBXW12):​c.406-1236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,988 control chromosomes in the GnomAD database, including 25,279 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 0.58 (25279 hom., cov: 31)
• Consequence: FBXW12 NM_207102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 6 publications found

Genes affected

FBXW12 (HGNC:20729): (F-box and WD repeat domain containing 12) Members of the F-box protein family, such as FBXW12, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603034), 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXW12	NM_207102.2	c.406-1236C>T		intron_variant	Intron 5 of 10	ENST00000296438.9	NP_996985.2
FBXW12	NM_001159929.1	c.349-1236C>T		intron_variant	Intron 4 of 9		NP_001153401.1
FBXW12	NM_001159927.1	c.405+1609C>T		intron_variant	Intron 5 of 9		NP_001153399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXW12	ENST00000296438.9	c.406-1236C>T		intron_variant	Intron 5 of 10	1	NM_207102.2	ENSP00000296438.5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87615 AN: 151870 Hom.: 25233 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.577 AC: 87722 AN: 151988 Hom.: 25279 Cov.: 31 AF XY: 0.582 AC XY: 43253 AN XY: 74268

African (AFR) AF: 0.602 AC: 24962 AN: 41450

American (AMR) AF: 0.602 AC: 9199 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3463 AN: 5166

South Asian (SAS) AF: 0.677 AC: 3261 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6355 AN: 10534

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36737 AN: 67960

Other (OTH) AF: 0.586 AC: 1235 AN: 2108

Alfa AF: 0.568 Hom.: 4523

Bravo AF: 0.577

Asia WGS AF: 0.634 AC: 2205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		-0.35
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: rs725310; hg19: chr3-48418571;