Variant 22-35756129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001349999.2(RBFOX2):c.1113C>T(p.Asp371Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000719 in 1,501,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

RBFOX2
NM_001349999.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.19

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 22-35756129-G-A is Benign according to our data. Variant chr22-35756129-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 750495.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX2	NM_001349999.2 linkuse as main transcript	c.1113C>T	p.Asp371Asp	synonymous_variant	11/14	ENST00000695854.1	NP_001336928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBFOX2	ENST00000695854.1 linkuse as main transcript	c.1113C>T	p.Asp371Asp	synonymous_variant	11/14		NM_001349999.2	ENSP00000512219.1	A0A8Q3WKT3
RBFOX2	ENST00000438146.7 linkuse as main transcript	c.1125C>T	p.Asp375Asp	synonymous_variant	11/14	1		ENSP00000413035.2	O43251-8
RBFOX2	ENST00000449924.6 linkuse as main transcript	c.912C>T	p.Asp304Asp	synonymous_variant	10/13	1		ENSP00000391670.2	O43251-10
RBFOX2	ENST00000414461.6 linkuse as main transcript	c.896+3759C>T		intron_variant		1		ENSP00000407855.2	O43251-4
RBFOX2	ENST00000695807.1 linkuse as main transcript	n.*365C>T		non_coding_transcript_exon_variant	11/15			ENSP00000512187.1	A0A8Q3SI31
RBFOX2	ENST00000695807.1 linkuse as main transcript	n.*365C>T		3_prime_UTR_variant	11/15			ENSP00000512187.1	A0A8Q3SI31
RBFOX2	ENST00000695805.1 linkuse as main transcript	n.*430+3759C>T		intron_variant				ENSP00000512185.1	A0A8Q3SI20

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

143112

Hom.:

AF XY:

0.0000393

AC XY:

AN XY:

76390

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.0000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000851

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000734

AC:

AN:

1349100

Hom.:

Cov.:

AF XY:

0.0000736

AC XY:

AN XY:

665750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000672

Gnomad4 AMR exome

AF:

0.0000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000300

Gnomad4 SAS exome

AF:

0.0000140

Gnomad4 FIN exome

AF:

0.0000417

Gnomad4 NFE exome

AF:

0.0000877

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000389

Hom.:

Bravo

AF:

0.0000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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