rs236796

Positions:

• chr17-15577303-A-G

Variant summary

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

The NM_001282540.2(FBXW10B):​c.2007-8273T>C 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 152,006 control chromosomes in the GnomAD database, including 8,002 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 (8002 hom., cov: 29)
• Consequence: FBXW10B NM_001282540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXW10B	NM_001282540.2	c.2007-8273T>C		intron_variant			NP_001269469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000251537	ENST00000455584.2	c.2778-3120T>C		intron_variant		2		ENSP00000402644.2
FBXW10B	ENST00000395667.7	c.2007-8273T>C		intron_variant		5		ENSP00000379026.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33176 AN: 151894 Hom.: 7973 Cov.: 29

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.219 AC: 33248 AN: 152006 Hom.: 8002 Cov.: 29 AF XY: 0.220 AC XY: 16317 AN XY: 74306

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.0688

Gnomad4 FIN AF: 0.0449

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.181

Alfa AF: 0.138 Hom.: 537

Bravo AF: 0.253

Asia WGS AF: 0.274 AC: 951 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.31

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: rs236796; hg19: chr17-15480617;