rs236796

Variant names:

• chr17-15577303-A-G
• rs236796
• ENST00000455584.2:c.2778-3120T>C

Variant summary

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

The ENST00000455584.2(ENSG00000251537):​c.2778-3120T>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: ENSG00000251537 ENST00000455584.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• 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=-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 rank	MANE	Protein	UniProt
FBXW10B	NM_001282540.2	c.2007-8273T>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.2778-3120T>C		intron_variant	Intron 16 of 16	2		ENSP00000402644.2
FBXW10B	ENST00000395667.7	c.2007-8273T>C		intron_variant	Intron 11 of 12	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

African (AFR) AF: 0.570 AC: 23550 AN: 41346

American (AMR) AF: 0.227 AC: 3460 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2618 AN: 5156

South Asian (SAS) AF: 0.0688 AC: 332 AN: 4828

European-Finnish (FIN) AF: 0.0449 AC: 476 AN: 10602

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0321 AC: 2182 AN: 68014

Other (OTH) AF: 0.181 AC: 382 AN: 2116

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
PhyloP100		-0.94

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: rs236796; hg19: chr17-15480617;