rs150282906

Variant names:

• chr17-79106690-G-A
• rs150282906
• NM_001350451.2:c.321C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001350451.2(RBFOX3):​c.321C>T​(p.Pro107Pro) variant causes a synonymous change. The variant allele was found at a frequency of 0.00154 in 1,489,880 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (26 hom.)
• Consequence: RBFOX3 NM_001350451.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.48

Genes affected

RBFOX3 (HGNC:27097): (RNA binding fox-1 homolog 3) This gene encodes a member of the RNA-binding FOX protein family which is involved in the regulation of alternative splicing of pre-mRNA. The protein has an N-terminal proline-rich region, an RNA recognition motif (RRM) domain, and a C-terminal alanine-rich region. This gene produces the neuronal nuclei (NeuN) antigen that has been widely used as a marker for post-mitotic neurons. This gene has its highest expression in the central nervous system and plays a prominent role in neural tissue development and regulation of adult brain function. Mutations in this gene have been associated with numerous neurological disorders. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 17-79106690-G-A is Benign according to our data. Variant chr17-79106690-G-A is described in ClinVar as [Benign]. Clinvar id is 238284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00288 (439/152284) while in subpopulation EAS AF= 0.0186 (96/5174). AF 95% confidence interval is 0.016. There are 5 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 439 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.321C>T	p.Pro107Pro	synonymous_variant	Exon 6 of 15	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1	c.321C>T	p.Pro107Pro	synonymous_variant	Exon 6 of 15		NM_001350451.2	ENSP00000510395.1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 439 AN: 152164 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00380 AC: 361 AN: 95036 Hom.: 2 AF XY: 0.00335 AC XY: 173 AN XY: 51602

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0239

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0148

Gnomad SAS exome AF: 0.000209

Gnomad FIN exome AF: 0.00258

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00319

GnomAD4 exome AF: 0.00139 AC: 1853 AN: 1337596 Hom.: 26 Cov.: 31 AF XY: 0.00131 AC XY: 866 AN XY: 658904

Gnomad4 AFR exome AF: 0.000260

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0270

Gnomad4 SAS exome AF: 0.000172

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00218

GnomAD4 genome AF: 0.00288 AC: 439 AN: 152284 Hom.: 5 Cov.: 33 AF XY: 0.00329 AC XY: 245 AN XY: 74464

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0186

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000687 Hom.: 0

Bravo AF: 0.00405

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

RBFOX3-related disorder Benign:1

Mar 13, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Idiopathic generalized epilepsy Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.86

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: rs150282906; hg19: chr17-77102772;