NM_018723.4:c.271-16602C>G

Variant names:

• chr16-7563175-C-G
• rs6500986
• NM_018723.4:c.271-16602C>G

Variant summary

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

The NM_018723.4(RBFOX1):​c.271-16602C>G 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 151,962 control chromosomes in the GnomAD database, including 21,523 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 (21523 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.271-16602C>G		intron_variant	Intron 5 of 15	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.331-16602C>G		intron_variant	Intron 2 of 13	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.271-16602C>G		intron_variant	Intron 5 of 15	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.331-16602C>G		intron_variant	Intron 2 of 13	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80120 AN: 151842 Hom.: 21506 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.528 AC: 80191 AN: 151962 Hom.: 21523 Cov.: 32 AF XY: 0.525 AC XY: 38982 AN XY: 74284

African (AFR) AF: 0.510 AC: 21138 AN: 41430

American (AMR) AF: 0.569 AC: 8698 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1899 AN: 3470

East Asian (EAS) AF: 0.186 AC: 959 AN: 5164

South Asian (SAS) AF: 0.518 AC: 2491 AN: 4810

European-Finnish (FIN) AF: 0.490 AC: 5166 AN: 10550

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38025 AN: 67952

Other (OTH) AF: 0.527 AC: 1112 AN: 2112

Alfa AF: 0.387 Hom.: 948

Bravo AF: 0.529

Asia WGS AF: 0.384 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		0.10
Mutation Taster		=99/1	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: rs6500986; hg19: chr16-7613177;