1-224114151-C-A

Variant names:

• chr1-224114151-C-A
• rs143831581
• NM_015176.4:c.22C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_015176.4(FBXO28):​c.22C>A​(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,544,000 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (18 hom.)
• Consequence: FBXO28 NM_015176.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.907
• Publications: 6 publications found

Genes affected

FBXO28 (HGNC:29046): (F-box protein 28) Members of the F-box protein family, such as FBXO28, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXO28 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 100

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000293922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 1-224114151-C-A is Benign according to our data. Variant chr1-224114151-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2639924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.907 with no splicing effect.
• BS2: High AC in GnomAd4 at 184 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015176.4. 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
	FBXO28	NM_015176.4	MANE Select	c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 5	NP_055991.1	Q9NVF7-1
	FBXO28	NM_001136115.3		c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 4	NP_001129587.1	Q9NVF7-2
	FBXO28	NR_049764.2		n.41C>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO28	ENST00000366862.10	TSL:1 MANE Select	c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 5	ENSP00000355827.5	Q9NVF7-1
	FBXO28	ENST00000424254.6	TSL:1	c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 4	ENSP00000416888.2	Q9NVF7-2
	FBXO28	ENST00000523990.1	TSL:2	n.22C>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000430632.1	B4E0H5

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152192 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00778

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00302 AC: 444 AN: 147098 AF XY: 0.00301

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00936

Gnomad ASJ exome AF: 0.000371

Gnomad EAS exome AF: 0.00232

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000253

Gnomad OTH exome AF: 0.00191

GnomAD4 exome AF: 0.000986 AC: 1372 AN: 1391690 Hom.: 18 Cov.: 35 AF XY: 0.00115 AC XY: 792 AN XY: 685886

African (AFR) AF: 0.0000639 AC: 2 AN: 31316

American (AMR) AF: 0.00839 AC: 295 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.000282 AC: 7 AN: 24830

East Asian (EAS) AF: 0.00900 AC: 320 AN: 35550

South Asian (SAS) AF: 0.00695 AC: 545 AN: 78468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48254

Middle Eastern (MID) AF: 0.00211 AC: 9 AN: 4262

European-Non Finnish (NFE) AF: 0.000121 AC: 130 AN: 1076232

Other (OTH) AF: 0.00111 AC: 64 AN: 57598

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152310 Hom.: 1 Cov.: 33 AF XY: 0.00137 AC XY: 102 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41560

American (AMR) AF: 0.00777 AC: 119 AN: 15306

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

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5182

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

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: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.000819 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.91
PromoterAI		-0.054	Neutral
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: rs143831581; hg19: chr1-224301853;