16-6690261-T-C

Variant names:

• chr16-6690261-T-C
• rs7197712
• NM_018723.4:c.-16+35611T>C

Variant summary

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

The ENST00000550418.6(RBFOX1):​c.-16+35611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,140 control chromosomes in the GnomAD database, including 1,910 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 0.11 (1910 hom., cov: 32)
• Consequence: RBFOX1 ENST00000550418.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550418.6. 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
	RBFOX1	NM_018723.4	MANE Select	c.-16+35611T>C		intron	N/A	NP_061193.2
	RBFOX1	NM_001415887.1		c.582+35611T>C		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.582+35611T>C		intron	N/A	NP_001402817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.-16+35611T>C		intron	N/A	ENSP00000450031.1
	RBFOX1	ENST00000553186.5	TSL:1	c.-16+35611T>C		intron	N/A	ENSP00000447753.1
	RBFOX1	ENST00000551752.5	TSL:1	c.-16+35611T>C		intron	N/A	ENSP00000447281.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17266 AN: 152022 Hom.: 1907 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.114 AC: 17289 AN: 152140 Hom.: 1910 Cov.: 32 AF XY: 0.116 AC XY: 8624 AN XY: 74404

African (AFR) AF: 0.236 AC: 9806 AN: 41498

American (AMR) AF: 0.119 AC: 1820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2145 AN: 5136

South Asian (SAS) AF: 0.153 AC: 736 AN: 4818

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2124 AN: 67996

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0630 Hom.: 1639

Bravo AF: 0.126

Asia WGS AF: 0.269 AC: 932 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.35
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: rs7197712; hg19: chr16-6740262;