NM_001350451.2:c.-74+30187T>C

Variant names:

• chr17-79277537-A-G
• rs898533
• NM_001350451.2:c.-74+30187T>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.-74+30187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,216 control chromosomes in the GnomAD database, including 1,704 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 0.15 (1704 hom., cov: 33)
• Consequence: RBFOX3 NM_001350451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 8 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, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	NM_001350451.2	MANE Select	c.-74+30187T>C		intron	N/A	NP_001337380.1	A0A8I5KWJ3
	RBFOX3	NM_001385804.1		c.-74+30187T>C		intron	N/A	NP_001372733.1
	RBFOX3	NM_001385805.1		c.-74+30187T>C		intron	N/A	NP_001372734.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	ENST00000693108.1	MANE Select	c.-74+30187T>C		intron	N/A	ENSP00000510395.1	A0A8I5KWJ3
	RBFOX3	ENST00000857749.1		c.-74+30187T>C		intron	N/A	ENSP00000527808.1
	RBFOX3	ENST00000583458.5	TSL:5	c.-74+30187T>C		intron	N/A	ENSP00000464186.1	J3QRF4

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22866 AN: 152098 Hom.: 1704 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.150 AC: 22871 AN: 152216 Hom.: 1704 Cov.: 33 AF XY: 0.150 AC XY: 11146 AN XY: 74410

African (AFR) AF: 0.148 AC: 6164 AN: 41534

American (AMR) AF: 0.155 AC: 2366 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1164 AN: 5164

South Asian (SAS) AF: 0.163 AC: 787 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1307 AN: 10598

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10083 AN: 68016

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.150 Hom.: 5034

Bravo AF: 0.152

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.68
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: rs898533; hg19: chr17-77273619;