NM_001163315.3:c.1822+36396A>G

Variant names:

• chr5-107984529-T-C
• rs10793832
• NM_001163315.3:c.1822+36396A>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+36396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,108 control chromosomes in the GnomAD database, including 4,300 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 0.23 (4300 hom., cov: 32)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1822+36396A>G		intron_variant	Intron 7 of 8	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5	c.1822+36396A>G		intron_variant	Intron 7 of 7		XP_005272105.1
FBXL17	XM_011543574.4	c.1822+36396A>G		intron_variant	Intron 7 of 7		XP_011541876.1
FBXL17	XM_011543575.3	c.1823-26394A>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+36396A>G		intron_variant	Intron 7 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.829+36396A>G		intron_variant	Intron 6 of 6	1		ENSP00000418111.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34361 AN: 151990 Hom.: 4294 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.226 AC: 34383 AN: 152108 Hom.: 4300 Cov.: 32 AF XY: 0.226 AC XY: 16797 AN XY: 74370

African (AFR) AF: 0.133 AC: 5515 AN: 41532

American (AMR) AF: 0.206 AC: 3143 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.0848 AC: 439 AN: 5178

South Asian (SAS) AF: 0.234 AC: 1124 AN: 4810

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19374 AN: 67958

Other (OTH) AF: 0.229 AC: 484 AN: 2110

Alfa AF: 0.160 Hom.: 362

Bravo AF: 0.216

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		-0.44
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: rs10793832; hg19: chr5-107320230; COSMIC: COSV62859988;