rs17720191

Positions:

• chr5-148410158-G-A

Variant summary

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

The NM_205836.3(FBXO38):​c.963-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,522 control chromosomes in the GnomAD database, including 12,344 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 0.38 (12323 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21 hom.)
• Consequence: FBXO38 NM_205836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

Genes affected

FBXO38 (HGNC:28844): (F-box protein 38) This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO38	NM_205836.3	c.963-477G>A		intron_variant		ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10	c.963-477G>A		intron_variant		5	NM_205836.3	ENSP00000342023	P3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58244 AN: 151804 Hom.: 12294 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.263 AC: 158 AN: 600 Hom.: 21 AF XY: 0.268 AC XY: 84 AN XY: 314

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.384 AC: 58321 AN: 151922 Hom.: 12323 Cov.: 32 AF XY: 0.390 AC XY: 29007 AN XY: 74284

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.355

Alfa AF: 0.297 Hom.: 6240

Bravo AF: 0.397

Asia WGS AF: 0.546 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17720191; hg19: chr5-147789721;