rs9518587

Variant names:

• chr13-101859005-T-C
• rs9518587
• NM_004115.4:c.408+9720A>G

Variant summary

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

The NM_004115.4(FGF14):​c.408+9720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,098 control chromosomes in the GnomAD database, including 1,826 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 0.15 (1826 hom., cov: 32)
• Consequence: FGF14 NM_004115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_004115.4	c.408+9720A>G		intron_variant	Intron 3 of 4	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143.5	c.408+9720A>G		intron_variant	Intron 3 of 4	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22140 AN: 151980 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.146 AC: 22141 AN: 152098 Hom.: 1826 Cov.: 32 AF XY: 0.146 AC XY: 10846 AN XY: 74354

African (AFR) AF: 0.0851 AC: 3536 AN: 41528

American (AMR) AF: 0.140 AC: 2136 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.137 AC: 709 AN: 5170

South Asian (SAS) AF: 0.182 AC: 877 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1436 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12231 AN: 67942

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.165 Hom.: 3162

Bravo AF: 0.142

Asia WGS AF: 0.141 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.61
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs9518587; hg19: chr13-102511355;