22-35770446-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349999.2(RBFOX2):c.664-2097C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,024 control chromosomes in the GnomAD database, including 2,988 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 (2988 hom., cov: 32)
• Consequence: RBFOX2 NM_001349999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

Genes affected

RBFOX2 (HGNC:9906): (RNA binding fox-1 homolog 2) This gene is one of several human genes similar to the C. elegans gene Fox-1. This gene encodes an RNA binding protein that is thought to be a key regulator of alternative exon splicing in the nervous system and other cell types. The protein binds to a conserved UGCAUG element found downstream of many alternatively spliced exons and promotes inclusion of the alternative exon in mature transcripts. The protein also interacts with the estrogen receptor 1 transcription factor and regulates estrogen receptor 1 transcriptional activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX2	NM_001349999.2	c.664-2097C>G		intron_variant		ENST00000695854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX2	ENST00000695854.1	c.664-2097C>G		intron_variant			NM_001349999.2	P3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26597 AN: 151906 Hom.: 2978 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.175 AC: 26645 AN: 152024 Hom.: 2988 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74318

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.0997

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0756 Hom.: 96

Bravo AF: 0.182

Asia WGS AF: 0.101 AC: 351 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.45
Dann	Benign	0.69

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: rs5755943; hg19: chr22-36166493;