ENST00000376131.9:c.208+217525T>C

Variant names:

• chr13-102183946-A-G
• rs9805437
• ENST00000376131.9:c.208+217525T>C

Variant summary

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

The ENST00000376131.9(FGF14):​c.208+217525T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 152,232 control chromosomes in the GnomAD database, including 1,141 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 0.096 (1141 hom., cov: 33)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 2 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: Ambry Genetics, Orphanet
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376131.9. 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.208+217525T>C		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.208+217525T>C		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.91+217525T>C		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.208+217525T>C		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.91+217525T>C		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-60+182499T>C		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14636 AN: 152114 Hom.: 1140 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0963 AC: 14664 AN: 152232 Hom.: 1141 Cov.: 33 AF XY: 0.0961 AC XY: 7156 AN XY: 74426

African (AFR) AF: 0.211 AC: 8743 AN: 41524

American (AMR) AF: 0.0760 AC: 1162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4816

European-Finnish (FIN) AF: 0.0471 AC: 501 AN: 10626

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3177 AN: 68010

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0632 Hom.: 784

Bravo AF: 0.101

Asia WGS AF: 0.0580 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9805437;

hg19: chr13-102836296;