22-35894660-C-T

Position:

• chr22-35894660-C-T

Variant summary

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

The NM_001349999.2(RBFOX2):​c.237+44187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,990 control chromosomes in the GnomAD database, including 5,684 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 0.22 (5684 hom., cov: 31)
• Consequence: RBFOX2 NM_001349999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX2	NM_001349999.2	c.237+44187G>A		intron_variant		ENST00000695854.1	NP_001336928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX2	ENST00000695854.1	c.237+44187G>A		intron_variant			NM_001349999.2	ENSP00000512219.1
RBFOX2	ENST00000438146.7	c.237+44187G>A		intron_variant		1		ENSP00000413035.2
RBFOX2	ENST00000695807.1	n.-34+44187G>A		intron_variant				ENSP00000512187.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33284 AN: 151872 Hom.: 5650 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.220 AC: 33372 AN: 151990 Hom.: 5684 Cov.: 31 AF XY: 0.212 AC XY: 15775 AN XY: 74308

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.183

Alfa AF: 0.0813 Hom.: 134

Bravo AF: 0.234

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5755979; hg19: chr22-36290707;