rs11107

Variant names:

• chr22-32479203-G-A
• rs11107
• NM_012179.4:c.345G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-32479203-G-A
• chr22-32479203-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_Moderate BP6_Very_Strong BA1

The NM_001257990.2(FBXO7):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,613,402 control chromosomes in the GnomAD database, including 136,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13649 hom., cov: 30)
  • Exomes 𝑓: 0.40 (123110 hom.)
• Consequence: FBXO7 NM_001257990.2 start_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0270
• Publications: 56 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 -14 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 25 codons. Genomic position: 32479273. Lost 0.059 part of the original CDS.
• BP6: Variant 22-32479203-G-A is Benign according to our data. Variant chr22-32479203-G-A is described in ClinVar as Benign. ClinVar VariationId is 195275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257990.2. 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
	FBXO7	NM_012179.4	MANE Select	c.345G>A	p.Met115Ile	missense	Exon 2 of 9	NP_036311.3
	FBXO7	NM_001257990.2		c.3G>A	p.Met1?	start_lost	Exon 2 of 9	NP_001244919.1
	FBXO7	NM_001033024.2		c.108G>A	p.Met36Ile	missense	Exon 2 of 9	NP_001028196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.345G>A	p.Met115Ile	missense	Exon 2 of 9	ENSP00000266087.7
	FBXO7	ENST00000397426.5	TSL:2	c.3G>A	p.Met1?	start_lost	Exon 2 of 9	ENSP00000380571.1
	FBXO7	ENST00000444207.1	TSL:2	c.3G>A	p.Met1?	start_lost	Exon 2 of 3	ENSP00000404388.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63089 AN: 151522 Hom.: 13628 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.453 AC: 113761 AN: 251364 AF XY: 0.447

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.402 AC: 588283 AN: 1461758 Hom.: 123110 Cov.: 49 AF XY: 0.405 AC XY: 294181 AN XY: 727172

African (AFR) AF: 0.380 AC: 12724 AN: 33474

American (AMR) AF: 0.595 AC: 26600 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 10621 AN: 26136

East Asian (EAS) AF: 0.736 AC: 29230 AN: 39698

South Asian (SAS) AF: 0.466 AC: 40236 AN: 86252

European-Finnish (FIN) AF: 0.469 AC: 25037 AN: 53416

Middle Eastern (MID) AF: 0.421 AC: 2429 AN: 5768

European-Non Finnish (NFE) AF: 0.374 AC: 416275 AN: 1111904

Other (OTH) AF: 0.416 AC: 25131 AN: 60388

GnomAD4 genome AF: 0.416 AC: 63145 AN: 151644 Hom.: 13649 Cov.: 30 AF XY: 0.425 AC XY: 31503 AN XY: 74086

African (AFR) AF: 0.387 AC: 15998 AN: 41306

American (AMR) AF: 0.505 AC: 7707 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3466

East Asian (EAS) AF: 0.687 AC: 3512 AN: 5112

South Asian (SAS) AF: 0.459 AC: 2214 AN: 4820

European-Finnish (FIN) AF: 0.496 AC: 5202 AN: 10486

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25773 AN: 67886

Other (OTH) AF: 0.401 AC: 847 AN: 2114

Alfa AF: 0.394 Hom.: 42932

Bravo AF: 0.418

TwinsUK AF: 0.361 AC: 1340

ALSPAC AF: 0.373 AC: 1437

ESP6500AA AF: 0.372 AC: 1640

ESP6500EA AF: 0.372 AC: 3202

ExAC AF: 0.440 AC: 53403

Asia WGS AF: 0.594 AC: 2063 AN: 3478

EpiCase AF: 0.374

EpiControl AF: 0.375

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Parkinsonian-pyramidal syndrome (5)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.6
DANN	Benign	0.39
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.082	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.027
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.089
Sift	Benign	0.22	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.010
MutPred		0.053		Gain of glycosylation at S114 (P = 0.0537)
MPC		0.070
ClinPred		0.0057	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.078
Mutation Taster		=120/80	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: rs11107; hg19: chr22-32875190; COSMIC: COSV56678154;