NM_001350451.2:c.-33-54973A>G

Variant names:

• chr17-79170721-T-C
• rs898528
• NM_001350451.2:c.-33-54973A>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.-33-54973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,054 control chromosomes in the GnomAD database, including 42,713 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 0.74 (42713 hom., cov: 30)
• Consequence: RBFOX3 NM_001350451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.-33-54973A>G		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.-33-54973A>G		intron_variant	Intron 4 of 14		NM_001350451.2	ENSP00000510395.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112554 AN: 151936 Hom.: 42672 Cov.: 30

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.741 AC: 112653 AN: 152054 Hom.: 42713 Cov.: 30 AF XY: 0.738 AC XY: 54868 AN XY: 74324

African (AFR) AF: 0.915 AC: 37941 AN: 41482

American (AMR) AF: 0.636 AC: 9707 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4164 AN: 5172

South Asian (SAS) AF: 0.790 AC: 3812 AN: 4824

European-Finnish (FIN) AF: 0.648 AC: 6839 AN: 10558

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45785 AN: 67960

Other (OTH) AF: 0.721 AC: 1521 AN: 2110

Alfa AF: 0.690 Hom.: 41750

Bravo AF: 0.745

Asia WGS AF: 0.801 AC: 2787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		-0.96
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: rs898528; hg19: chr17-77166803; COSMIC: COSV70562885;