chr5-15515680-T-C

Position:

• chr5-15515680-T-C

Variant summary

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

The NM_012304.5(FBXL7):​c.37+14967T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,318 control chromosomes in the GnomAD database, including 330 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 0.027 (330 hom., cov: 32)
• Consequence: FBXL7 NM_012304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL7	NM_012304.5	c.37+14967T>C		intron_variant		ENST00000504595.2	NP_036436.1
FBXL7	NM_001278317.2	c.-105+13957T>C		intron_variant			NP_001265246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL7	ENST00000504595.2	c.37+14967T>C		intron_variant		1	NM_012304.5	ENSP00000423630	P1
FBXL7	ENST00000510662.1	c.-105+13957T>C		intron_variant		1		ENSP00000425184

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4044 AN: 152202 Hom.: 332 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0265 AC: 4044 AN: 152318 Hom.: 330 Cov.: 32 AF XY: 0.0286 AC XY: 2131 AN XY: 74468

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0156 Hom.: 6

Bravo AF: 0.0273

Asia WGS AF: 0.161 AC: 558 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	7.6
DANN	Benign	0.53

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: rs680474; hg19: chr5-15515789;