22-32491011-T-C

Position:

• chr22-32491011-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012179.4(FBXO7):​c.872-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 976,158 control chromosomes in the GnomAD database, including 90,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14049 hom., cov: 32)
  • Exomes 𝑓: 0.42 (76558 hom.)
• Consequence: FBXO7 NM_012179.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0320

Genes affected

FBXO7 (HGNC:13586): (F-box protein 7) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

FBXO7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-32491011-T-C is Benign according to our data. Variant chr22-32491011-T-C is described in ClinVar as [Benign]. Clinvar id is 1296267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO7	NM_012179.4	c.872-75T>C		intron_variant		ENST00000266087.12	NP_036311.3
FBXO7	NM_001033024.2	c.635-75T>C		intron_variant			NP_001028196.1
FBXO7	NM_001257990.2	c.530-75T>C		intron_variant			NP_001244919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087.12	c.872-75T>C		intron_variant		1	NM_012179.4	ENSP00000266087.7

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64181 AN: 151944 Hom.: 14029 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.419 AC: 345326 AN: 824096 Hom.: 76558 Cov.: 11 AF XY: 0.420 AC XY: 182481 AN XY: 434574

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.422 AC: 64236 AN: 152062 Hom.: 14049 Cov.: 32 AF XY: 0.432 AC XY: 32090 AN XY: 74344

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.405

Alfa AF: 0.396 Hom.: 1954

Bravo AF: 0.425

Asia WGS AF: 0.595 AC: 2066 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.69

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: rs738982; hg19: chr22-32886998; COSMIC: COSV56676775;