rs17135875

Variant names:

• chr7-102878584-T-C
• rs17135875
• ENST00000440067.4:c.1659-134A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FBXL13	NM_001394494.2	c.1659-134A>G		intron_variant	Intron 15 of 20		NP_001381423.1
FBXL13	NM_145032.3	c.1389-134A>G		intron_variant	Intron 14 of 19		NP_659469.3
FBXL13	NM_001287150.2	c.1389-134A>G		intron_variant	Intron 14 of 18		NP_001274079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4	c.1659-134A>G		intron_variant	Intron 15 of 20	3		ENSP00000390126.2

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

African (AFR) AF: 0.384 AC: 3200 AN: 8330

American (AMR) AF: 0.140 AC: 1222 AN: 8714

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 1772 AN: 9818

East Asian (EAS) AF: 0.00269 AC: 60 AN: 22282

South Asian (SAS) AF: 0.121 AC: 951 AN: 7884

European-Finnish (FIN) AF: 0.188 AC: 3932 AN: 20892

Middle Eastern (MID) AF: 0.224 AC: 329 AN: 1466

European-Non Finnish (NFE) AF: 0.192 AC: 45514 AN: 236638

Other (OTH) AF: 0.202 AC: 3781 AN: 18730

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

African (AFR) AF: 0.377 AC: 15640 AN: 41450

American (AMR) AF: 0.183 AC: 2801 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3468

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5188

South Asian (SAS) AF: 0.113 AC: 544 AN: 4826

European-Finnish (FIN) AF: 0.184 AC: 1940 AN: 10570

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12931 AN: 67954

Other (OTH) AF: 0.231 AC: 487 AN: 2110

Alfa AF: 0.206 Hom.: 6000

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
PhyloP100		-1.6
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: rs17135875; hg19: chr7-102519031;