chr17-79277537-A-G

Position:

• chr17-79277537-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.-74+30187T>C		intron_variant		ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1	c.-74+30187T>C		intron_variant			NM_001350451.2	ENSP00000510395

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

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.155

Alfa AF: 0.151 Hom.: 2849

Bravo AF: 0.152

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs898533; hg19: chr17-77273619;