rs12917722

Positions:

• chr16-30937076-A-G
• chr16-30937076-A-T

Variant summary

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

The NM_001382779.1(FBXL19):​c.1302-5040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,942 control chromosomes in the GnomAD database, including 11,170 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 0.33 (11170 hom., cov: 31)
• Consequence: FBXL19 NM_001382779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

Genes affected

FBXL19 (HGNC:25300): (F-box and leucine rich repeat protein 19) This gene encodes a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases. The encoded protein is reported to bind to the transmembrane receptor interleukin 1 receptor-like 1 and regulate its ubiquitination and degradation. This protein has been linked to the regulation of pulmonary inflammation and psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL19	NM_001382779.1	c.1302-5040A>G		intron_variant		ENST00000338343.10	NP_001369708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL19	ENST00000338343.10	c.1302-5040A>G		intron_variant		5	NM_001382779.1	ENSP00000339712	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50716 AN: 151824 Hom.: 11168 Cov.: 31

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.334 AC: 50717 AN: 151942 Hom.: 11170 Cov.: 31 AF XY: 0.336 AC XY: 24942 AN XY: 74276

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.398

Alfa AF: 0.392 Hom.: 3790

Bravo AF: 0.333

Asia WGS AF: 0.473 AC: 1647 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.55

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: rs12917722; hg19: chr16-30948397;