rs10418248

Positions:

• chr19-9827538-T-A
• chr19-9827538-T-C

Variant summary

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

The ENST00000585379.5(FBXL12):​c.-74+253A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,828 control chromosomes in the GnomAD database, including 4,642 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 0.18 (4642 hom., cov: 31)
• Consequence: FBXL12 ENST00000585379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

Genes affected

FBXL12 (HGNC:13611): (F-box and leucine rich repeat protein 12) Members of the F-box protein family, such as FBXL12, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL12	ENST00000585379.5	c.-74+253A>T		intron_variant		2		ENSP00000467359

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26928 AN: 151708 Hom.: 4619 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.178 AC: 27010 AN: 151828 Hom.: 4642 Cov.: 31 AF XY: 0.176 AC XY: 13049 AN XY: 74234

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.156

Alfa AF: 0.118 Hom.: 310

Bravo AF: 0.194

Asia WGS AF: 0.167 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10418248; hg19: chr19-9938214;