16-87381644-T-C

Variant names:

• chr16-87381644-T-C
• rs933717
• NM_024735.5:c.340+1761A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024735.5(FBXO31):​c.340+1761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,158 control chromosomes in the GnomAD database, including 17,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (17209 hom., cov: 33)
• Consequence: FBXO31 NM_024735.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-87381644-T-C is Benign according to our data. Variant chr16-87381644-T-C is described in ClinVar as [Benign]. Clinvar id is 1239788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO31	NM_024735.5	c.340+1761A>G		intron_variant	Intron 1 of 8	ENST00000311635.12	NP_079011.3
FBXO31	NM_001282683.2	c.-177+8093A>G		intron_variant	Intron 2 of 9		NP_001269612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO31	ENST00000311635.12	c.340+1761A>G		intron_variant	Intron 1 of 8	1	NM_024735.5	ENSP00000310841.4

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65745 AN: 152040 Hom.: 17188 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.432 AC: 65789 AN: 152158 Hom.: 17209 Cov.: 33 AF XY: 0.456 AC XY: 33955 AN XY: 74384

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.480

Alfa AF: 0.449 Hom.: 17895

Bravo AF: 0.426

Asia WGS AF: 0.871 AC: 3023 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29044928) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.69

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: rs933717; hg19: chr16-87415250;