chr19-9827538-T-A

Variant names:

• chr19-9827538-T-A
• rs10418248
• ENST00000585379.5:c.-74+253A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL12	ENST00000585379.5	c.-74+253A>T		intron_variant	Intron 1 of 2	2		ENSP00000467359.1

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

African (AFR) AF: 0.447 AC: 18428 AN: 41258

American (AMR) AF: 0.127 AC: 1933 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3470

East Asian (EAS) AF: 0.0487 AC: 250 AN: 5138

South Asian (SAS) AF: 0.166 AC: 800 AN: 4814

European-Finnish (FIN) AF: 0.0574 AC: 608 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4376 AN: 67958

Other (OTH) AF: 0.156 AC: 329 AN: 2110

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
PhyloP100		-0.25
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10418248; hg19: chr19-9938214;