16-30930083-C-T

Variant names:

• chr16-30930083-C-T
• rs781616493
• NM_001382779.1:c.800C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001282351.1(FBXL19):​c.-77C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000373 in 1,610,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: FBXL19 NM_001282351.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05354613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282351.1. 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.800C>T	p.Pro267Leu	missense	Exon 7 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001282351.1		c.-77C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 11	NP_001269280.1	H3BVB1
	FBXL19	NM_001099784.3		c.860C>T	p.Pro287Leu	missense	Exon 7 of 11	NP_001093254.2	Q6PCT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.800C>T	p.Pro267Leu	missense	Exon 7 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.533C>T	p.Pro178Leu	missense	Exon 6 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000471231.6	TSL:2	c.-77C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 11	ENSP00000458033.1	H3BVB1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000855 AC: 21 AN: 245744 AF XY: 0.0000822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.000806

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000370 AC: 54 AN: 1457844 Hom.: 0 Cov.: 32 AF XY: 0.0000386 AC XY: 28 AN XY: 724622

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.000225 AC: 10 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.000806 AC: 21 AN: 26042

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39598

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52906

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1109304

Other (OTH) AF: 0.0000665 AC: 4 AN: 60182

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152362 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74516

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.000327 AC: 5 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000579 AC: 7

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	0.078
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Benign	0.79
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.099
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.082
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.050	T
Polyphen		0.71	P
Vest4		0.31
MutPred		0.13		Loss of glycosylation at P287 (P = 0.0343)
MVP		0.043
MPC		2.2
ClinPred		0.073	T
GERP RS		5.3
Varity_R		0.054
gMVP		0.30
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs781616493; hg19: chr16-30941404; COSMIC: COSV100608627; COSMIC: COSV100608627;