5-107964954-T-C

Variant names:

• chr5-107964954-T-C
• rs885624
• NM_001163315.3:c.1822+55971A>G

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+55971A>G variant causes a intron change. The variant allele was found at a frequency of 0.307 in 151,890 control chromosomes in the GnomAD database, including 7,299 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 0.31 (7299 hom., cov: 32)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1822+55971A>G		intron_variant	Intron 7 of 8	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5	c.1822+55971A>G		intron_variant	Intron 7 of 7		XP_005272105.1
FBXL17	XM_011543574.4	c.1823-18258A>G		intron_variant	Intron 7 of 7		XP_011541876.1
FBXL17	XM_011543575.3	c.1823-6819A>G		intron_variant	Intron 7 of 7		XP_011541877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1822+55971A>G		intron_variant	Intron 7 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.829+55971A>G		intron_variant	Intron 6 of 6	1		ENSP00000418111.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46617 AN: 151772 Hom.: 7280 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.307 AC: 46677 AN: 151890 Hom.: 7299 Cov.: 32 AF XY: 0.310 AC XY: 22996 AN XY: 74240

African (AFR) AF: 0.331 AC: 13714 AN: 41448

American (AMR) AF: 0.237 AC: 3609 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1198 AN: 3462

East Asian (EAS) AF: 0.407 AC: 2103 AN: 5162

South Asian (SAS) AF: 0.381 AC: 1829 AN: 4804

European-Finnish (FIN) AF: 0.313 AC: 3303 AN: 10564

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19991 AN: 67896

Other (OTH) AF: 0.296 AC: 623 AN: 2108

Alfa AF: 0.300 Hom.: 29633

Bravo AF: 0.303

Asia WGS AF: 0.360 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.80
PhyloP100		3.8
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: rs885624; hg19: chr5-107300655; COSMIC: COSV62859927;