ENST00000376131.9:c.209-200857T>C

Variant names:

• chr13-102076153-A-G
• rs12865694
• ENST00000376131.9:c.209-200857T>C

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-200857T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,184 control chromosomes in the GnomAD database, including 4,015 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 0.20 (4015 hom., cov: 32)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 1 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 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.209-200857T>C		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.209-207325T>C		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.92-200857T>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.209-200857T>C		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.92-200857T>C		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-59-200857T>C		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29937 AN: 152066 Hom.: 4015 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.197 AC: 29926 AN: 152184 Hom.: 4015 Cov.: 32 AF XY: 0.190 AC XY: 14143 AN XY: 74392

African (AFR) AF: 0.0499 AC: 2073 AN: 41540

American (AMR) AF: 0.167 AC: 2561 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5192

South Asian (SAS) AF: 0.131 AC: 629 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2450 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20409 AN: 67964

Other (OTH) AF: 0.200 AC: 423 AN: 2110

Alfa AF: 0.243 Hom.: 652

Bravo AF: 0.187

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.1
DANN	Benign	0.90
PhyloP100		0.24
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: rs12865694;

hg19: chr13-102728503;