22-32491011-T-C

Variant names:

• chr22-32491011-T-C
• rs738982
• NM_012179.4:c.872-75T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• parkinsonian-pyramidal syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012179.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	NM_012179.4	MANE Select	c.872-75T>C		intron	N/A	NP_036311.3
	FBXO7	NM_001033024.2		c.635-75T>C		intron	N/A	NP_001028196.1
	FBXO7	NM_001257990.2		c.530-75T>C		intron	N/A	NP_001244919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.872-75T>C		intron	N/A	ENSP00000266087.7
	FBXO7	ENST00000484607.1	TSL:1	n.542-75T>C		intron	N/A
	FBXO7	ENST00000492535.1	TSL:5	n.3890T>C		non_coding_transcript_exon	Exon 5 of 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

African (AFR) AF: 0.402 AC: 8334 AN: 20736

American (AMR) AF: 0.595 AC: 24851 AN: 41752

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 8799 AN: 21740

East Asian (EAS) AF: 0.740 AC: 27062 AN: 36554

South Asian (SAS) AF: 0.467 AC: 33503 AN: 71678

European-Finnish (FIN) AF: 0.467 AC: 23460 AN: 50208

Middle Eastern (MID) AF: 0.415 AC: 1690 AN: 4074

European-Non Finnish (NFE) AF: 0.374 AC: 201213 AN: 538126

Other (OTH) AF: 0.418 AC: 16414 AN: 39228

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

African (AFR) AF: 0.407 AC: 16894 AN: 41468

American (AMR) AF: 0.507 AC: 7746 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1452 AN: 3472

East Asian (EAS) AF: 0.689 AC: 3562 AN: 5172

South Asian (SAS) AF: 0.461 AC: 2224 AN: 4824

European-Finnish (FIN) AF: 0.497 AC: 5258 AN: 10584

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25799 AN: 67958

Other (OTH) AF: 0.405 AC: 855 AN: 2110

Alfa AF: 0.396 Hom.: 2015

Bravo AF: 0.425

Asia WGS AF: 0.595 AC: 2066 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism (auto)

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