rs1062746

Positions:

• chr16-87331044-T-C

Variant summary

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

The NM_024735.5(FBXO31):​c.*244A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 492,278 control chromosomes in the GnomAD database, including 33,863 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 0.35 (10245 hom., cov: 32)
  • Exomes 𝑓: 0.35 (23618 hom.)
• Consequence: FBXO31 NM_024735.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5	c.*244A>G		3_prime_UTR_variant	9/9	ENST00000311635.12
FBXO31	NM_001282683.2	c.*244A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12	c.*244A>G		3_prime_UTR_variant	9/9	1	NM_024735.5	P1
FBXO31	ENST00000618298.6	c.*244A>G		3_prime_UTR_variant	9/9	5
FBXO31	ENST00000636077.2	c.*244A>G		3_prime_UTR_variant	10/10	5
FBXO31	ENST00000565593.1	c.*570A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53893 AN: 151992 Hom.: 10244 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.351 AC: 119397 AN: 340168 Hom.: 23618 Cov.: 3 AF XY: 0.340 AC XY: 60389 AN XY: 177704

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.354 AC: 53911 AN: 152110 Hom.: 10245 Cov.: 32 AF XY: 0.342 AC XY: 25390 AN XY: 74348

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.357

Alfa AF: 0.411 Hom.: 12768

Bravo AF: 0.356

Asia WGS AF: 0.131 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.45

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: rs1062746; hg19: chr16-87364650;