rs938283

Variant names:

• chr17-79472416-T-C
• rs938283
• NM_001350451.2:c.-175+10038A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350451.2(RBFOX3):​c.-175+10038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,158 control chromosomes in the GnomAD database, including 1,992 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 0.16 (1992 hom., cov: 32)
• Consequence: RBFOX3 NM_001350451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 20 publications found

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]

RBFOX3 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.-175+10038A>G		intron_variant	Intron 2 of 14	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1	c.-175+10038A>G		intron_variant	Intron 2 of 14		NM_001350451.2	ENSP00000510395.1
RBFOX3	ENST00000583458.5	c.-175+10038A>G		intron_variant	Intron 1 of 13	5		ENSP00000464186.1
RBFOX3	ENST00000584778.5	c.-175+10038A>G		intron_variant	Intron 2 of 13	5		ENSP00000462007.1
RBFOX3	ENST00000580155.5	c.-175+10038A>G		intron_variant	Intron 2 of 14	2		ENSP00000463653.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23993 AN: 152040 Hom.: 1993 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.158 AC: 24003 AN: 152158 Hom.: 1992 Cov.: 32 AF XY: 0.158 AC XY: 11736 AN XY: 74386

African (AFR) AF: 0.120 AC: 4999 AN: 41514

American (AMR) AF: 0.153 AC: 2339 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.162 AC: 840 AN: 5188

South Asian (SAS) AF: 0.140 AC: 674 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2190 AN: 10582

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11575 AN: 67984

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.165 Hom.: 3158

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs938283; hg19: chr17-77468498;