chr16-30927867-C-T

Variant names:

• chr16-30927867-C-T
• rs201252774
• NM_001382779.1:c.531C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001382779.1(FBXL19):​c.531C>T​(p.Gly177Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 1,528,946 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (62 hom.)
• Consequence: FBXL19 NM_001382779.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0260
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.044).
• BP6: Variant 16-30927867-C-T is Benign according to our data. Variant chr16-30927867-C-T is described in ClinVar as Benign. ClinVar VariationId is 774720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.531C>T	p.Gly177Gly	synonymous	Exon 5 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001099784.3		c.591C>T	p.Gly197Gly	synonymous	Exon 5 of 11	NP_001093254.2	Q6PCT2-1
	FBXL19	NM_001382780.1		c.597C>T	p.Gly199Gly	synonymous	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.531C>T	p.Gly177Gly	synonymous	Exon 5 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.393C>T	p.Gly131Gly	synonymous	Exon 4 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000562319.7	TSL:2	c.591C>T	p.Gly197Gly	synonymous	Exon 5 of 11	ENSP00000455529.2	Q6PCT2-1

Frequencies

GnomAD3 genomes AF: 0.00631 AC: 960 AN: 152208 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00546 AC: 712 AN: 130410 AF XY: 0.00541

Gnomad AFR exome AF: 0.000590

Gnomad AMR exome AF: 0.00795

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00258

Gnomad NFE exome AF: 0.00936

Gnomad OTH exome AF: 0.00710

GnomAD4 exome AF: 0.00821 AC: 11301 AN: 1376620 Hom.: 62 Cov.: 34 AF XY: 0.00816 AC XY: 5540 AN XY: 678898

African (AFR) AF: 0.00119 AC: 36 AN: 30322

American (AMR) AF: 0.00767 AC: 224 AN: 29194

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 26 AN: 24078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.00113 AC: 87 AN: 76784

European-Finnish (FIN) AF: 0.00227 AC: 108 AN: 47552

Middle Eastern (MID) AF: 0.000832 AC: 4 AN: 4810

European-Non Finnish (NFE) AF: 0.00974 AC: 10437 AN: 1071206

Other (OTH) AF: 0.00665 AC: 379 AN: 56962

GnomAD4 genome AF: 0.00630 AC: 960 AN: 152326 Hom.: 5 Cov.: 33 AF XY: 0.00608 AC XY: 453 AN XY: 74482

African (AFR) AF: 0.00166 AC: 69 AN: 41564

American (AMR) AF: 0.00686 AC: 105 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

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

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.00329 AC: 35 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00948 AC: 645 AN: 68022

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00681 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.5
DANN	Benign	0.81
PhyloP100		0.026
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs201252774; hg19: chr16-30939188; COSMIC: COSV57941485; COSMIC: COSV57941485;