16-30937076-A-G

Variant names:

• chr16-30937076-A-G
• rs12917722
• NM_001382779.1:c.1302-5040A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382779.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	NM_001382779.1	MANE Select	c.1302-5040A>G		intron	N/A	NP_001369708.1
	FBXL19	NM_001099784.3		c.1362-5040A>G		intron	N/A	NP_001093254.2
	FBXL19	NM_001382780.1		c.1239-5040A>G		intron	N/A	NP_001369709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.1302-5040A>G		intron	N/A	ENSP00000339712.4
	FBXL19	ENST00000427128.5	TSL:1	c.1035-5040A>G		intron	N/A	ENSP00000397913.1
	FBXL19	ENST00000562319.7	TSL:2	c.1362-5040A>G		intron	N/A	ENSP00000455529.2

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

African (AFR) AF: 0.0787 AC: 3261 AN: 41414

American (AMR) AF: 0.400 AC: 6107 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1867 AN: 3464

East Asian (EAS) AF: 0.903 AC: 4671 AN: 5172

South Asian (SAS) AF: 0.199 AC: 961 AN: 4820

European-Finnish (FIN) AF: 0.436 AC: 4594 AN: 10544

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27872 AN: 67956

Other (OTH) AF: 0.398 AC: 838 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		0.41
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: rs12917722; hg19: chr16-30948397;