2-73265273-G-A

Position:

• chr2-73265273-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001371389.2(FBXO41):​c.1564+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000936 in 1,592,304 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00055 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (20 hom.)
• Consequence: FBXO41 NM_001371389.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.512

Genes affected

FBXO41 (HGNC:29409): (F-box protein 41) This gene encodes a member of the F-box protein family, which is characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one of the four subunits of the SCF ubiquitin protein ligase complex that plays a role in phosphorylation-dependent ubiquitination. F-box proteins are divided into three classes depending on the interaction substrate domain each contains in addition to the F-box motif: FBXW proteins contain WD-40 domains, FBXL proteins contain leucine-rich repeats, and FBXO proteins contain either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the FBXO class. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-73265273-G-A is Benign according to our data. Variant chr2-73265273-G-A is described in ClinVar as [Benign]. Clinvar id is 769564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO41	NM_001371389.2	c.1564+9C>T		intron_variant		ENST00000520530.3	NP_001358318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO41	ENST00000520530.3	c.1564+9C>T		intron_variant		5	NM_001371389.2	ENSP00000430968.2
FBXO41	ENST00000295133.9	c.1564+9C>T		intron_variant		1		ENSP00000295133.6
FBXO41	ENST00000521871.5	c.1564+9C>T		intron_variant		5		ENSP00000428646.1

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152174 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00179 AC: 404 AN: 226040 Hom.: 6 AF XY: 0.00250 AC XY: 309 AN XY: 123832

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.000388

Gnomad ASJ exome AF: 0.000115

Gnomad EAS exome AF: 0.000451

Gnomad SAS exome AF: 0.0125

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.000714

GnomAD4 exome AF: 0.000976 AC: 1406 AN: 1440012 Hom.: 20 Cov.: 31 AF XY: 0.00136 AC XY: 974 AN XY: 714998

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000433

Gnomad4 ASJ exome AF: 0.0000401

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.000130

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152292 Hom.: 2 Cov.: 33 AF XY: 0.000779 AC XY: 58 AN XY: 74470

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000247 Hom.: 0

Bravo AF: 0.000291

Asia WGS AF: 0.00231 AC: 8 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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs371450076; hg19: chr2-73492401;