NM_001163315.3:c.1822+43223T>C

Variant names:

• chr5-107977702-A-G
• rs10900900
• NM_001163315.3:c.1822+43223T>C

Variant summary

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

The NM_001163315.3(FBXL17):​c.1822+43223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,178 control chromosomes in the GnomAD database, including 5,099 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 0.25 (5099 hom., cov: 33)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 2 publications found

Genes affected

FBXL17 (HGNC:13615): (F-box and leucine rich repeat protein 17) Members of the F-box protein family, such as FBXL17, 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163315.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL17	NM_001163315.3	MANE Select	c.1822+43223T>C		intron	N/A	NP_001156787.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL17	ENST00000542267.7	TSL:1 MANE Select	c.1822+43223T>C		intron	N/A	ENSP00000437464.2
	FBXL17	ENST00000496714.2	TSL:1	c.829+43223T>C		intron	N/A	ENSP00000418111.2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38487 AN: 152060 Hom.: 5089 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.253 AC: 38521 AN: 152178 Hom.: 5099 Cov.: 33 AF XY: 0.253 AC XY: 18794 AN XY: 74382

African (AFR) AF: 0.210 AC: 8710 AN: 41530

American (AMR) AF: 0.216 AC: 3300 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3167 AN: 10582

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19784 AN: 67982

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.271 Hom.: 9035

Bravo AF: 0.246

Asia WGS AF: 0.160 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		0.38
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: rs10900900; hg19: chr5-107313403; COSMIC: COSV62859966;