rs57017013

Positions:

• chr15-63599762-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001367807.1(FBXL22):​c.354-935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 986,342 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0079 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: FBXL22 NM_001367807.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

Genes affected

FBXL22 (HGNC:27537): (F-box and leucine rich repeat protein 22) This gene encodes a member of the F-box protein family. This F-box protein interacts with S-phase kinase-associated protein 1A and cullin in order to form SCF complexes which function as ubiquitin ligases.[provided by RefSeq, Sep 2010]

USP3-AS1 (HGNC:44140): (USP3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00789 (1202/152318) while in subpopulation AFR AF= 0.0278 (1154/41556). AF 95% confidence interval is 0.0264. There are 18 homozygotes in gnomad4. There are 574 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL22	NM_001367807.1	c.354-935G>A		intron_variant		ENST00000638704.2
USP3-AS1	NR_034080.1	n.239+827C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL22	ENST00000638704.2	c.354-935G>A		intron_variant		2	NM_001367807.1	P1
USP3-AS1	ENST00000649220.2	n.207+827C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00785 AC: 1195 AN: 152200 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000603 AC: 503 AN: 834024 Hom.: 2 Cov.: 28 AF XY: 0.000605 AC XY: 233 AN XY: 385224

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000605

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000393

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.00789 AC: 1202 AN: 152318 Hom.: 18 Cov.: 33 AF XY: 0.00771 AC XY: 574 AN XY: 74472

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00883 Hom.: 2

Bravo AF: 0.00895

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs57017013; hg19: chr15-63891961;