rs767727470

Variant names:

• chr16-7333037-T-C
• rs767727470
• NM_145893.3:c.36T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-7333037-T-C
• chr16-7333037-T-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_145893.3(RBFOX1):​c.36T>C​(p.Tyr12Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: RBFOX1 NM_145893.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.286
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-7333037-T-C is Benign according to our data. Variant chr16-7333037-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1584701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.286 with no splicing effect.
• BS2: High AC in GnomAd4 at 8 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145893.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.36T>C	p.Tyr12Tyr	synonymous	Exon 1 of 14	NP_665900.1	Q9NWB1-5
	RBFOX1	NM_018723.4	MANE Select	c.28-185110T>C		intron	N/A	NP_061193.2
	RBFOX1	NM_145891.3		c.36T>C	p.Tyr12Tyr	synonymous	Exon 1 of 13	NP_665898.1	Q9NWB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.36T>C	p.Tyr12Tyr	synonymous	Exon 1 of 14	ENSP00000347855.4	Q9NWB1-5
	RBFOX1	ENST00000311745.9	TSL:1	c.36T>C	p.Tyr12Tyr	synonymous	Exon 1 of 13	ENSP00000309117.5	Q9NWB1-2
	RBFOX1	ENST00000436368.6	TSL:1	c.36T>C	p.Tyr12Tyr	synonymous	Exon 1 of 13	ENSP00000402745.2	Q9NWB1-4

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250862 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461636 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727126

African (AFR) AF: 0.0000598 AC: 2 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111876

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74316

African (AFR) AF: 0.0000965 AC: 4 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Idiopathic generalized epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		-0.29
PromoterAI		-0.036	Neutral

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: rs767727470; hg19: chr16-7383038;