rs5995177

Positions:

• chr22-35913505-G-A
• chr22-35913505-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.237+25342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 148,076 control chromosomes in the GnomAD database, including 3,701 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 0.17 (3701 hom., cov: 28)
• Consequence: RBFOX2 NM_001349999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX2	NM_001349999.2	c.237+25342C>T		intron_variant		ENST00000695854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX2	ENST00000695854.1	c.237+25342C>T		intron_variant			NM_001349999.2	P3

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25115 AN: 147976 Hom.: 3680 Cov.: 28

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0922

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.170 AC: 25183 AN: 148076 Hom.: 3701 Cov.: 28 AF XY: 0.165 AC XY: 11921 AN XY: 72240

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0262 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5995177; hg19: chr22-36309553;