rs9783820

Variant names:

• chr17-18757008-C-A
• rs9783820
• NM_001267585.2:c.1232+854C>A

Variant summary

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

The NM_001267585.2(FBXW10):​c.1232+854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 150,864 control chromosomes in the GnomAD database, including 19,120 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 0.50 (19120 hom., cov: 30)
• Consequence: FBXW10 NM_001267585.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXW10	NM_001267585.2	c.1232+854C>A		intron_variant	Intron 6 of 13	ENST00000395665.9	NP_001254514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXW10	ENST00000395665.9	c.1232+854C>A		intron_variant	Intron 6 of 13	1	NM_001267585.2	ENSP00000379025.4
FBXW10	ENST00000301938.4	c.1232+854C>A		intron_variant	Intron 6 of 12	1		ENSP00000306937.4
FBXW10	ENST00000574478.1	n.*1287+854C>A		intron_variant	Intron 6 of 13	1		ENSP00000463552.1
FBXW10	ENST00000308799.8	c.1319+854C>A		intron_variant	Intron 5 of 11	2		ENSP00000310382.4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 74933 AN: 150746 Hom.: 19083 Cov.: 30

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.497 AC: 75017 AN: 150864 Hom.: 19120 Cov.: 30 AF XY: 0.490 AC XY: 36072 AN XY: 73648

African (AFR) AF: 0.484 AC: 19834 AN: 40938

American (AMR) AF: 0.465 AC: 7042 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1927 AN: 3466

East Asian (EAS) AF: 0.132 AC: 664 AN: 5044

South Asian (SAS) AF: 0.355 AC: 1690 AN: 4762

European-Finnish (FIN) AF: 0.508 AC: 5287 AN: 10404

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.543 AC: 36830 AN: 67806

Other (OTH) AF: 0.490 AC: 1023 AN: 2086

Alfa AF: 0.505 Hom.: 6833

Bravo AF: 0.491

Asia WGS AF: 0.274 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		0.67
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: rs9783820; hg19: chr17-18660321; COSMIC: COSV57315769;