rs72795979

Positions:

• chr5-107946647-T-C
• chr5-107946647-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542267.7(FBXL17):​c.1823-65468A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,590 control chromosomes in the GnomAD database, including 2,251 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 0.17 (2251 hom., cov: 28)
• Consequence: FBXL17 ENST00000542267.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1823-65468A>G		intron_variant		ENST00000542267.7	NP_001156787.2
FBXL17	XM_011543574.4	c.*6A>G		3_prime_UTR_variant	8/8		XP_011541876.1
FBXL17	XM_005272048.5	c.1823-65468A>G		intron_variant			XP_005272105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1823-65468A>G		intron_variant		1	NM_001163315.3	ENSP00000437464	P1
FBXL17	ENST00000496714.2	c.831-65468A>G		intron_variant		1		ENSP00000418111

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25224 AN: 151478 Hom.: 2240 Cov.: 28

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.167 AC: 25270 AN: 151590 Hom.: 2251 Cov.: 28 AF XY: 0.167 AC XY: 12372 AN XY: 74044

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.169

Alfa AF: 0.122 Hom.: 305

Bravo AF: 0.162

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.77
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs72795979; hg19: chr5-107282348;