rs151446

Variant names:

• chr17-15580535-A-G
• rs151446
• ENST00000455584.2:c.2778-6352T>C

Variant summary

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

The ENST00000455584.2(ENSG00000251537):​c.2778-6352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.20 (1906 hom., cov: 12)
• Consequence: ENSG00000251537 ENST00000455584.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 1 publications found

Genes affected

ENSG00000251537 (HGNC:):

FBXW10B (HGNC:14379): (F-box and WD repeat domain containing 10B) Members of the F-box protein family, such as FBXW10, 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXW10B	NM_001282540.2	c.2007-11505T>C		intron_variant	Intron 11 of 12		NP_001269469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000251537	ENST00000455584.2	c.2778-6352T>C		intron_variant	Intron 16 of 16	2		ENSP00000402644.2
FBXW10B	ENST00000395667.7	c.2007-11505T>C		intron_variant	Intron 11 of 12	5		ENSP00000379026.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 12430 AN: 63530 Hom.: 1901 Cov.: 12

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.196 AC: 12451 AN: 63644 Hom.: 1906 Cov.: 12 AF XY: 0.199 AC XY: 6126 AN XY: 30802

African (AFR) AF: 0.272 AC: 6715 AN: 24722

American (AMR) AF: 0.257 AC: 1848 AN: 7196

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 81 AN: 994

East Asian (EAS) AF: 0.498 AC: 1987 AN: 3990

South Asian (SAS) AF: 0.0718 AC: 175 AN: 2438

European-Finnish (FIN) AF: 0.0516 AC: 114 AN: 2208

Middle Eastern (MID) AF: 0.134 AC: 11 AN: 82

European-Non Finnish (NFE) AF: 0.0649 AC: 1365 AN: 21022

Other (OTH) AF: 0.179 AC: 130 AN: 728

Alfa AF: 0.0843 Hom.: 128

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	10
DANN	Benign	0.38
PhyloP100		0.60

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: rs151446; hg19: chr17-15483849;