rs12659622

Positions:

• chr5-15618072-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012304.5(FBXL7):​c.127+2000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,064 control chromosomes in the GnomAD database, including 621 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 0.085 (621 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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]

CTD-2350J17.1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL7	NM_012304.5	c.127+2000G>A		intron_variant		ENST00000504595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL7	ENST00000504595.2	c.127+2000G>A		intron_variant		1	NM_012304.5	P1
FBXL7	ENST00000510662.1	c.-15+2000G>A		intron_variant		1
CTD-2350J17.1	ENST00000509228.2	n.62+976C>T		intron_variant, non_coding_transcript_variant		2
CTD-2350J17.1	ENST00000671066.1	n.62-731C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12890 AN: 151946 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0847 AC: 12887 AN: 152064 Hom.: 621 Cov.: 32 AF XY: 0.0845 AC XY: 6282 AN XY: 74344

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.0876

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0856

Alfa AF: 0.104 Hom.: 1003

Bravo AF: 0.0820

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
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: rs12659622; hg19: chr5-15618181;