16-5435507-T-G

Position:

• chr16-5435507-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641259.1(RBFOX1):​c.220-31709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,098 control chromosomes in the GnomAD database, including 34,122 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 0.67 (34122 hom., cov: 32)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_001415887.1	c.340-31709T>G		intron_variant
RBFOX1	NM_001415888.1	c.340-31709T>G		intron_variant
RBFOX1	XM_017023318.3	c.340-31709T>G		intron_variant
RBFOX1	XM_024450303.2	c.340-163395T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000585867.2	c.220-31709T>G		intron_variant		2
RBFOX1	ENST00000641259.1	c.220-31709T>G		intron_variant
RBFOX1	ENST00000569895.3	n.305-31709T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101090 AN: 151980 Hom.: 34071 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.665 AC: 101197 AN: 152098 Hom.: 34122 Cov.: 32 AF XY: 0.668 AC XY: 49659 AN XY: 74340

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.650

Alfa AF: 0.580 Hom.: 3691

Bravo AF: 0.673

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs471459; hg19: chr16-5485508;