chr13-101930093-G-C

Variant names:

• chr13-101930093-G-C
• rs2476230
• ENST00000376131.9:c.209-54797C>G

Variant summary

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

The NM_175929.3(FGF14):​c.209-54797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,006 control chromosomes in the GnomAD database, including 15,975 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 (15975 hom., cov: 33)
• Consequence: FGF14 NM_175929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.40
• Publications: 4 publications found

Genes affected

FGF14 (HGNC:3671): (fibroblast growth factor 14) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

FGF14 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 27A

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spinocerebellar ataxia type 27

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175929.3. 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
	FGF14	NM_175929.3		c.209-54797C>G		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.209-61265C>G		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.92-54797C>G		intron	N/A	NP_001308874.1	A0A9L9PXK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376131.9	TSL:1	c.209-54797C>G		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.92-54797C>G		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-59-54797C>G		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58590 AN: 151888 Hom.: 15926 Cov.: 33

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.386 AC: 58696 AN: 152006 Hom.: 15975 Cov.: 33 AF XY: 0.387 AC XY: 28746 AN XY: 74314

African (AFR) AF: 0.733 AC: 30386 AN: 41460

American (AMR) AF: 0.415 AC: 6330 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3466

East Asian (EAS) AF: 0.727 AC: 3761 AN: 5174

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4812

European-Finnish (FIN) AF: 0.206 AC: 2179 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12541 AN: 67956

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.280 Hom.: 1069

Bravo AF: 0.421

Asia WGS AF: 0.522 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.020
DANN	Benign	0.42
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2476230; hg19: chr13-102582443;