rs11641750

Variant names:

• chr16-6304935-G-A
• rs11641750
• NM_018723.4:c.-126-12060G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-6304935-G-A
• chr16-6304935-G-C
• chr16-6304935-G-T

Variant summary

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

The NM_018723.4(RBFOX1):​c.-126-12060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 146,642 control chromosomes in the GnomAD database, including 23,510 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 0.53 (23510 hom., cov: 28)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-126-12060G>A		intron_variant	Intron 1 of 15	ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-126-12060G>A		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 77412 AN: 146556 Hom.: 23503 Cov.: 28

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.528 AC: 77432 AN: 146642 Hom.: 23510 Cov.: 28 AF XY: 0.533 AC XY: 38054 AN XY: 71368

African (AFR) AF: 0.181 AC: 6967 AN: 38576

American (AMR) AF: 0.577 AC: 8474 AN: 14684

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2447 AN: 3442

East Asian (EAS) AF: 0.609 AC: 2980 AN: 4894

South Asian (SAS) AF: 0.604 AC: 2770 AN: 4584

European-Finnish (FIN) AF: 0.749 AC: 7336 AN: 9796

Middle Eastern (MID) AF: 0.654 AC: 187 AN: 286

European-Non Finnish (NFE) AF: 0.662 AC: 44612 AN: 67428

Other (OTH) AF: 0.558 AC: 1146 AN: 2052

Alfa AF: 0.613 Hom.: 45431

Bravo AF: 0.488

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.62
PhyloP100		-0.71
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: rs11641750; hg19: chr16-6354936; COSMIC: COSV70566985;