rs75002042

Variant names:

• chr5-15669858-T-A
• rs75002042
• NM_012304.5:c.127+53786T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-15669858-T-A
• chr5-15669858-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012304.5(FBXL7):​c.127+53786T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,218 control chromosomes in the GnomAD database, including 1,235 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 0.078 (1235 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 publications found

Genes affected

FBXL7 (HGNC:13604): (F-box and leucine rich repeat protein 7) This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012304.5. 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
	FBXL7	NM_012304.5	MANE Select	c.127+53786T>A		intron	N/A	NP_036436.1	Q9UJT9-1
	FBXL7	NM_001278317.2		c.-15+53786T>A		intron	N/A	NP_001265246.1	Q9UJT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL7	ENST00000504595.2	TSL:1 MANE Select	c.127+53786T>A		intron	N/A	ENSP00000423630.1	Q9UJT9-1
	FBXL7	ENST00000510662.1	TSL:1	c.-15+53786T>A		intron	N/A	ENSP00000425184.1	Q9UJT9-2

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11803 AN: 152100 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00931

Gnomad OTH AF: 0.0569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0776 AC: 11817 AN: 152218 Hom.: 1235 Cov.: 32 AF XY: 0.0766 AC XY: 5698 AN XY: 74416

African (AFR) AF: 0.202 AC: 8378 AN: 41502

American (AMR) AF: 0.0321 AC: 491 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1831 AN: 5162

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4826

European-Finnish (FIN) AF: 0.00735 AC: 78 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00932 AC: 634 AN: 68018

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0113 Hom.: 16

Bravo AF: 0.0865

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.54
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs75002042; hg19: chr5-15669967;