chr17-18775235-C-T

Variant names:

• chr17-18775235-C-T
• rs4630608
• NM_001267585.2:c.2335+43C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FBXW10	NM_001267585.2	c.2335+43C>T		intron_variant	Intron 13 of 13	ENST00000395665.9	NP_001254514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXW10	ENST00000395665.9	c.2335+43C>T		intron_variant	Intron 13 of 13	1	NM_001267585.2	ENSP00000379025.4
FBXW10	ENST00000301938.4	c.2176+43C>T		intron_variant	Intron 12 of 12	1		ENSP00000306937.4
FBXW10	ENST00000574478.1	n.*2390+43C>T		intron_variant	Intron 13 of 13	1		ENSP00000463552.1
FBXW10	ENST00000308799.8	c.2365+2552C>T		intron_variant	Intron 11 of 11	2		ENSP00000310382.4

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

GnomAD2 exomes AF: 0.448 AC: 109305 AN: 243796 AF XY: 0.446

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 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

African (AFR) AF: 0.483 AC: 13580 AN: 28118

American (AMR) AF: 0.411 AC: 17847 AN: 43442

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 12853 AN: 24350

East Asian (EAS) AF: 0.267 AC: 10241 AN: 38308

South Asian (SAS) AF: 0.334 AC: 26510 AN: 79314

European-Finnish (FIN) AF: 0.456 AC: 24234 AN: 53158

Middle Eastern (MID) AF: 0.489 AC: 2556 AN: 5232

European-Non Finnish (NFE) AF: 0.502 AC: 435662 AN: 867598

Other (OTH) AF: 0.469 AC: 24152 AN: 51494

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

African (AFR) AF: 0.497 AC: 20583 AN: 41450

American (AMR) AF: 0.453 AC: 6916 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1353 AN: 5180

South Asian (SAS) AF: 0.307 AC: 1475 AN: 4808

European-Finnish (FIN) AF: 0.440 AC: 4632 AN: 10530

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34352 AN: 67976

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.494 Hom.: 54430

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
PhyloP100		-0.82
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: rs4630608; hg19: chr17-18678548; COSMIC: COSV57317927; COSMIC: COSV57317927;