Genetic Variant RBFOX2:c.1138-16C>T (chr22-35746577-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_001349999.2(RBFOX2):c.1138-16C>T variant causes a intron change. The variant allele was found at a frequency of 0.000051 in 1,509,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

RBFOX2
NM_001349999.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.76

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP6

Variant 22-35746577-G-A is Benign according to our data. Variant chr22-35746577-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3603974.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX2	NM_001349999.2 link	c.1138-16C>T		intron_variant	Intron 11 of 13	ENST00000695854.1	NP_001336928.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBFOX2	ENST00000695854.1 link	c.1138-16C>T	intron_variant	Intron 11 of 13		NM_001349999.2	ENSP00000512219.1	A0A8Q3WKT3
RBFOX2	ENST00000438146.7 link	c.1150-16C>T	intron_variant	Intron 11 of 13	1		ENSP00000413035.2	O43251-8
RBFOX2	ENST00000449924.6 link	c.937-16C>T	intron_variant	Intron 10 of 12	1		ENSP00000391670.2	O43251-10
RBFOX2	ENST00000414461.6 link	c.897-16C>T	intron_variant	Intron 9 of 11	1		ENSP00000407855.2	O43251-4
RBFOX2	ENST00000695807.1 link	n.*4105C>T	non_coding_transcript_exon_variant	Exon 13 of 15			ENSP00000512187.1	A0A8Q3SI31
RBFOX2	ENST00000695807.1 link	n.*4105C>T	3_prime_UTR_variant	Exon 13 of 15			ENSP00000512187.1	A0A8Q3SI31
RBFOX2	ENST00000695805.1 link	n.*431-16C>T	intron_variant	Intron 10 of 12			ENSP00000512185.1	A0A8Q3SI20

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

183960

Hom.:

AF XY:

0.0000200

AC XY:

AN XY:

99982

show subpopulations

Gnomad AFR exome

AF:

0.000463

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000142

Gnomad EAS exome

AF:

0.0000746

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000427

AC:

AN:

1357704

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

671684

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000432

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000115

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.000125

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000117

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over