NM_001350451.2:c.-33-29478G>A

Variant names:

• chr17-79145226-C-T
• rs7211029
• NM_001350451.2:c.-33-29478G>A

Variant summary

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

The NM_001350451.2(RBFOX3):​c.-33-29478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,120 control chromosomes in the GnomAD database, including 4,867 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 0.24 (4867 hom., cov: 33)
• Consequence: RBFOX3 NM_001350451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.-33-29478G>A		intron_variant	Intron 4 of 14	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1	c.-33-29478G>A		intron_variant	Intron 4 of 14		NM_001350451.2	ENSP00000510395.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36986 AN: 152002 Hom.: 4864 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00637

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.243 AC: 37015 AN: 152120 Hom.: 4867 Cov.: 33 AF XY: 0.239 AC XY: 17760 AN XY: 74354

African (AFR) AF: 0.196 AC: 8130 AN: 41496

American (AMR) AF: 0.189 AC: 2897 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.00658 AC: 34 AN: 5170

South Asian (SAS) AF: 0.160 AC: 768 AN: 4814

European-Finnish (FIN) AF: 0.263 AC: 2785 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20824 AN: 67990

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.255 Hom.: 875

Bravo AF: 0.233

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.69
PhyloP100		-1.6
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: rs7211029; hg19: chr17-77141308;