13-102058988-T-C

Variant names:

• chr13-102058988-T-C
• rs35700852
• ENST00000376131.9:c.209-183692A>G

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-183692A>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 151,418 control chromosomes in the GnomAD database, including 11,884 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 (11884 hom., cov: 31)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	NM_175929.3		c.209-183692A>G		intron	N/A	NP_787125.1
	FGF14	NM_001321939.2		c.209-190160A>G		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.92-183692A>G		intron	N/A	NP_001308874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376131.9	TSL:1	c.209-183692A>G		intron	N/A	ENSP00000365301.3
	FGF14	ENST00000418923.3	TSL:3	c.92-183692A>G		intron	N/A	ENSP00000516414.1
	FGF14	ENST00000706494.1		c.-59-183692A>G		intron	N/A	ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58462 AN: 151316 Hom.: 11880 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.386 AC: 58482 AN: 151418 Hom.: 11884 Cov.: 31 AF XY: 0.391 AC XY: 28909 AN XY: 73946

African (AFR) AF: 0.306 AC: 12642 AN: 41252

American (AMR) AF: 0.496 AC: 7543 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3554 AN: 5134

South Asian (SAS) AF: 0.417 AC: 2005 AN: 4804

European-Finnish (FIN) AF: 0.374 AC: 3871 AN: 10346

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.385 AC: 26161 AN: 67890

Other (OTH) AF: 0.406 AC: 854 AN: 2104

Alfa AF: 0.311 Hom.: 1221

Bravo AF: 0.390

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.60
PhyloP100		0.83
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: rs35700852; hg19: chr13-102711338;