rs5995177

Variant names:

• chr22-35913505-G-A
• rs5995177
• NM_001349999.2:c.237+25342C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-35913505-G-A
• chr22-35913505-G-C

Variant summary

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

The NM_001082578.4(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_001082578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 9 publications found

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]

RBFOX2 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082578.4. 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
	RBFOX2	NM_001349999.2	MANE Select	c.237+25342C>T		intron	N/A	NP_001336928.2
	RBFOX2	NM_001082578.4		c.237+25342C>T		intron	N/A	NP_001076047.2
	RBFOX2	NM_001082579.3		c.237+25342C>T		intron	N/A	NP_001076048.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX2	ENST00000695854.1	MANE Select	c.237+25342C>T		intron	N/A	ENSP00000512219.1
	RBFOX2	ENST00000438146.7	TSL:1	c.237+25342C>T		intron	N/A	ENSP00000413035.2
	RBFOX2	ENST00000359369.8	TSL:1	c.-34+25342C>T		intron	N/A	ENSP00000352328.4

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

African (AFR) AF: 0.400 AC: 15873 AN: 39694

American (AMR) AF: 0.0982 AC: 1466 AN: 14926

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 381 AN: 3432

East Asian (EAS) AF: 0.0381 AC: 190 AN: 4990

South Asian (SAS) AF: 0.0835 AC: 388 AN: 4644

European-Finnish (FIN) AF: 0.0492 AC: 500 AN: 10162

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0891 AC: 5968 AN: 66982

Other (OTH) AF: 0.146 AC: 299 AN: 2054

Alfa AF: 0.0262 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.31
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5995177; hg19: chr22-36309553;