rs17135875

Positions:

• chr7-102878584-T-C

Variant summary

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

The ENST00000440067.4(FBXL13):​c.1659-134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 486,818 control chromosomes in the GnomAD database, including 11,211 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 (4730 hom., cov: 32)
  • Exomes 𝑓: 0.18 (6481 hom.)
• Consequence: FBXL13 ENST00000440067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL13	NM_001394494.2	c.1659-134A>G		intron_variant		ENST00000440067.4
FBXL13	NR_105043.2	n.1685-134A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL13	ENST00000440067.4	c.1659-134A>G		intron_variant		3	NM_001394494.2	P2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35081 AN: 151944 Hom.: 4716 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.182 AC: 60761 AN: 334754 Hom.: 6481 AF XY: 0.182 AC XY: 30839 AN XY: 169692

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.00269

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.231 AC: 35136 AN: 152064 Hom.: 4730 Cov.: 32 AF XY: 0.228 AC XY: 16958 AN XY: 74340

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.231

Alfa AF: 0.206 Hom.: 727

Bravo AF: 0.238

Asia WGS AF: 0.0740 AC: 260 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.87

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: rs17135875; hg19: chr7-102519031;