chr17-18775235-C-T

Position:

• chr17-18775235-C-T

Variant summary

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

The NM_001267585.2(FBXW10):​c.2335+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,343,004 control chromosomes in the GnomAD database, including 155,201 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 0.48 (17737 hom., cov: 32)
  • Exomes 𝑓: 0.48 (137464 hom.)
• Consequence: FBXW10 NM_001267585.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

Genes affected

FBXW10 (HGNC:1211): (F-box and WD repeat domain containing 10) 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 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXW10	NM_001267585.2	c.2335+43C>T		intron_variant		ENST00000395665.9	NP_001254514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXW10	ENST00000395665.9	c.2335+43C>T		intron_variant		1	NM_001267585.2	ENSP00000379025	P2
FBXW10	ENST00000301938.4	c.2176+43C>T		intron_variant		1		ENSP00000306937	A2
FBXW10	ENST00000574478.1	c.*2390+43C>T		intron_variant, NMD_transcript_variant		1		ENSP00000463552
FBXW10	ENST00000308799.8	c.2365+2552C>T		intron_variant		2		ENSP00000310382	A2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72789 AN: 151872 Hom.: 17724 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.483

GnomAD3 exomes AF: 0.448 AC: 109305 AN: 243796 Hom.: 25243 AF XY: 0.446 AC XY: 58955 AN XY: 132240

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.272

Gnomad SAS exome AF: 0.336

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.477 AC: 567635 AN: 1191014 Hom.: 137464 Cov.: 16 AF XY: 0.471 AC XY: 285501 AN XY: 605596

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.479 AC: 72843 AN: 151990 Hom.: 17737 Cov.: 32 AF XY: 0.472 AC XY: 35044 AN XY: 74290

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.487

Alfa AF: 0.498 Hom.: 32456

Bravo AF: 0.483

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.54

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: rs4630608; hg19: chr17-18678548; COSMIC: COSV57317927; COSMIC: COSV57317927;