rs7205345

Variant names:

• chr16-7470252-C-G
• rs7205345
• NM_018723.4:c.28-47895C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-7470252-C-G
• chr16-7470252-C-T

Variant summary

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

The NM_001415887.1(RBFOX1):​c.625-47895C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,066 control chromosomes in the GnomAD database, including 17,832 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 0.48 (17832 hom., cov: 33)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 5 publications found

Genes affected

RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RBFOX1 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• autism susceptibility 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

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 (SAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415887.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.28-47895C>G		intron	N/A	NP_061193.2
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.88-47895C>G		intron	N/A	NP_665900.1
	RBFOX1	NM_001415887.1		c.625-47895C>G		intron	N/A	NP_001402816.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.28-47895C>G		intron	N/A	ENSP00000450031.1
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.88-47895C>G		intron	N/A	ENSP00000347855.4
	RBFOX1	ENST00000311745.9	TSL:1	c.88-47895C>G		intron	N/A	ENSP00000309117.5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73242 AN: 151948 Hom.: 17823 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.482 AC: 73293 AN: 152066 Hom.: 17832 Cov.: 33 AF XY: 0.483 AC XY: 35914 AN XY: 74340

African (AFR) AF: 0.459 AC: 19030 AN: 41476

American (AMR) AF: 0.506 AC: 7725 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2236 AN: 5136

South Asian (SAS) AF: 0.563 AC: 2716 AN: 4826

European-Finnish (FIN) AF: 0.473 AC: 5004 AN: 10578

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33065 AN: 67984

Other (OTH) AF: 0.509 AC: 1074 AN: 2112

Alfa AF: 0.474 Hom.: 2119

Bravo AF: 0.482

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7205345; hg19: chr16-7520254;