rs202132610

Variant names:

• chr16-30928546-C-T
• rs202132610
• NM_001382779.1:c.707C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-30928546-C-T
• chr16-30928546-C-G

Variant summary

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

The NM_001282351.1(FBXL19):​c.-172C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,607,972 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 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000041 (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: 0.511
• Publications: 4 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=0.030860871).

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.707C>T	p.Pro236Leu	missense	Exon 6 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001282351.1		c.-172C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 11	NP_001269280.1	H3BVB1
	FBXL19	NM_001099784.3		c.767C>T	p.Pro256Leu	missense	Exon 6 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.707C>T	p.Pro236Leu	missense	Exon 6 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.522+47C>T		intron	N/A	ENSP00000397913.1	H7C112
	FBXL19	ENST00000471231.6	TSL:2	c.-172C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 11	ENSP00000458033.1	H3BVB1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD2 exomes AF: 0.0000336 AC: 8 AN: 237948 AF XY: 0.0000385

Gnomad AFR exome AF: 0.000422

Gnomad AMR exome AF: 0.0000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000930

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1455708 Hom.: 0 Cov.: 32 AF XY: 0.0000428 AC XY: 31 AN XY: 723944

African (AFR) AF: 0.000786 AC: 26 AN: 33098

American (AMR) AF: 0.000159 AC: 7 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 38916

South Asian (SAS) AF: 0.00 AC: 0 AN: 85456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1109258

Other (OTH) AF: 0.0000333 AC: 2 AN: 60074

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152264 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74436

African (AFR) AF: 0.000530 AC: 22 AN: 41544

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.000227

ExAC AF: 0.0000580 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	0.093
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.51
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.065
Sift	Benign	0.042	D
Sift4G	Benign	0.096	T
Polyphen		0.58	P
Vest4		0.28
MVP		0.043
MPC		0.020
ClinPred		0.065	T
GERP RS		5.0
Varity_R		0.084
gMVP		0.47
Mutation Taster		=285/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs202132610; hg19: chr16-30939867; COSMIC: COSV57940426; COSMIC: COSV57940426;