rs764049236

Variant names:

• chr16-30927890-C-G
• rs764049236
• NM_001382779.1:c.554C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-30927890-C-G
• chr16-30927890-C-T
• chr16-30927890-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382779.1(FBXL19):​c.554C>G​(p.Pro185Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,534,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P185A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FBXL19 NM_001382779.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05834329).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	NM_001382779.1	MANE Select	c.554C>G	p.Pro185Arg	missense	Exon 5 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001099784.3		c.614C>G	p.Pro205Arg	missense	Exon 5 of 11	NP_001093254.2	Q6PCT2-1
	FBXL19	NM_001382780.1		c.620C>G	p.Pro207Arg	missense	Exon 5 of 11	NP_001369709.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.554C>G	p.Pro185Arg	missense	Exon 5 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.416C>G	p.Pro139Arg	missense	Exon 4 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000562319.7	TSL:2	c.614C>G	p.Pro205Arg	missense	Exon 5 of 11	ENSP00000455529.2	Q6PCT2-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1381996 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 682222

African (AFR) AF: 0.00 AC: 0 AN: 30378

American (AMR) AF: 0.00 AC: 0 AN: 29154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23690

East Asian (EAS) AF: 0.00 AC: 0 AN: 36414

South Asian (SAS) AF: 0.00 AC: 0 AN: 76368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1075472

Other (OTH) AF: 0.00 AC: 0 AN: 57148

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.1
DANN	Benign	0.81
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.13
Sift	Benign	0.23	T
Sift4G	Benign	0.25	T
Polyphen		0.40	B
Vest4		0.21
MutPred		0.25		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.043
MPC		0.021
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.043
gMVP		0.24
Mutation Taster		=271/29	polymorphism

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: rs764049236; hg19: chr16-30939211;