chr16-5989766-C-G

Variant names:

• chr16-5989766-C-G
• rs748987
• ENST00000641259.1:c.351+122431C>G

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.351+122431C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 150,730 control chromosomes in the GnomAD database, including 17,882 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 (17882 hom., cov: 27)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.471+122431C>G		intron_variant	Intron 4 of 19		NP_001402816.1
RBFOX1	NM_001415888.1	c.471+122431C>G		intron_variant	Intron 4 of 17		NP_001402817.1
RBFOX1	XM_017023318.3	c.471+122431C>G		intron_variant	Intron 4 of 19		XP_016878807.1
RBFOX1	XM_024450303.2	c.432+122431C>G		intron_variant	Intron 3 of 18		XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.351+122431C>G		intron_variant	Intron 4 of 19			ENSP00000493041.1
RBFOX1	ENST00000569895.3	n.436+122431C>G		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 72989 AN: 150612 Hom.: 17885 Cov.: 27

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.484 AC: 73016 AN: 150730 Hom.: 17882 Cov.: 27 AF XY: 0.477 AC XY: 35128 AN XY: 73582

African (AFR) AF: 0.533 AC: 21813 AN: 40910

American (AMR) AF: 0.467 AC: 7066 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3464

East Asian (EAS) AF: 0.351 AC: 1781 AN: 5072

South Asian (SAS) AF: 0.442 AC: 2094 AN: 4740

European-Finnish (FIN) AF: 0.389 AC: 4042 AN: 10378

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33111 AN: 67766

Other (OTH) AF: 0.482 AC: 1001 AN: 2076

Alfa AF: 0.490 Hom.: 2236

Bravo AF: 0.492

Asia WGS AF: 0.375 AC: 1302 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		-0.066

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748987; hg19: chr16-6039767;