NM_001350451.2:c.-33-11784T>C

Variant names:

• chr17-79127532-A-G
• rs2707047
• NM_001350451.2:c.-33-11784T>C

Variant summary

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

The NM_001350451.2(RBFOX3):​c.-33-11784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,014 control chromosomes in the GnomAD database, including 19,201 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 0.49 (19201 hom., cov: 32)
• Consequence: RBFOX3 NM_001350451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.-33-11784T>C		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.-33-11784T>C		intron_variant	Intron 4 of 14		NM_001350451.2	ENSP00000510395.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74070 AN: 151896 Hom.: 19205 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.487 AC: 74087 AN: 152014 Hom.: 19201 Cov.: 32 AF XY: 0.481 AC XY: 35742 AN XY: 74312

African (AFR) AF: 0.369 AC: 15310 AN: 41438

American (AMR) AF: 0.428 AC: 6537 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3470

East Asian (EAS) AF: 0.160 AC: 824 AN: 5154

South Asian (SAS) AF: 0.332 AC: 1599 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5830 AN: 10586

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40613 AN: 67950

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.546 Hom.: 11888

Bravo AF: 0.472

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.43
PhyloP100		-0.15
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: rs2707047; hg19: chr17-77123614;