chr16-87381644-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

FBXO31 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive 45

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024735.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	NM_024735.5	MANE Select	c.340+1761A>G		intron	N/A	NP_079011.3
	FBXO31	NM_001282683.2		c.-177+8093A>G		intron	N/A	NP_001269612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.340+1761A>G		intron	N/A	ENSP00000310841.4
	FBXO31	ENST00000636077.2	TSL:5	c.340+1761A>G		intron	N/A	ENSP00000490402.2
	FBXO31	ENST00000618298.6	TSL:5	c.-177+8093A>G		intron	N/A	ENSP00000479703.1

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

African (AFR) AF: 0.194 AC: 8055 AN: 41520

American (AMR) AF: 0.609 AC: 9313 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5182

South Asian (SAS) AF: 0.862 AC: 4160 AN: 4828

European-Finnish (FIN) AF: 0.555 AC: 5874 AN: 10580

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29437 AN: 67980

Other (OTH) AF: 0.480 AC: 1012 AN: 2110

Alfa AF: 0.432 Hom.: 31204

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs933717; hg19: chr16-87415250;