rs2007979

Variant names:

• chr17-79127567-G-A
• rs2007979
• NM_001350451.2:c.-33-11819C>T

Variant summary

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

The ENST00000693108.1(RBFOX3):​c.-33-11819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,092 control chromosomes in the GnomAD database, including 3,197 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 0.18 (3197 hom., cov: 33)
• Consequence: RBFOX3 ENST00000693108.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000693108.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	NM_001350451.2	MANE Select	c.-33-11819C>T		intron	N/A	NP_001337380.1
	RBFOX3	NM_001385804.1		c.-33-11819C>T		intron	N/A	NP_001372733.1
	RBFOX3	NM_001385805.1		c.-33-11819C>T		intron	N/A	NP_001372734.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	ENST00000693108.1	MANE Select	c.-33-11819C>T		intron	N/A	ENSP00000510395.1
	RBFOX3	ENST00000583458.5	TSL:5	c.-33-11819C>T		intron	N/A	ENSP00000464186.1
	RBFOX3	ENST00000582043.5	TSL:5	c.-33-11819C>T		intron	N/A	ENSP00000463964.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27459 AN: 151974 Hom.: 3193 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.181 AC: 27482 AN: 152092 Hom.: 3197 Cov.: 33 AF XY: 0.177 AC XY: 13138 AN XY: 74344

African (AFR) AF: 0.326 AC: 13526 AN: 41450

American (AMR) AF: 0.122 AC: 1872 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3472

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5178

South Asian (SAS) AF: 0.248 AC: 1199 AN: 4826

European-Finnish (FIN) AF: 0.0649 AC: 686 AN: 10570

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8939 AN: 67986

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.149 Hom.: 6060

Bravo AF: 0.190

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		0.10
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: rs2007979; hg19: chr17-77123649;