chr16-7667119-A-C

Variant names:

• chr16-7667119-A-C
• rs3785214
• NM_018723.4:c.930+2151A>C

Variant summary

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

The NM_018723.4(RBFOX1):​c.930+2151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,016 control chromosomes in the GnomAD database, including 12,700 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 0.39 (12700 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.930+2151A>C		intron_variant	Intron 13 of 15	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.951-4438A>C		intron_variant	Intron 9 of 13	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.930+2151A>C		intron_variant	Intron 13 of 15	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.951-4438A>C		intron_variant	Intron 9 of 13	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58755 AN: 151900 Hom.: 12701 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.387 AC: 58763 AN: 152016 Hom.: 12700 Cov.: 32 AF XY: 0.382 AC XY: 28353 AN XY: 74302

African (AFR) AF: 0.215 AC: 8933 AN: 41458

American (AMR) AF: 0.484 AC: 7402 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3462

East Asian (EAS) AF: 0.117 AC: 607 AN: 5166

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4812

European-Finnish (FIN) AF: 0.376 AC: 3979 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33306 AN: 67964

Other (OTH) AF: 0.393 AC: 827 AN: 2106

Alfa AF: 0.457 Hom.: 5757

Bravo AF: 0.387

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		0.65
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: rs3785214; hg19: chr16-7717121; COSMIC: COSV60979283;