ENST00000376131.9:c.209-249079C>A

Variant names:

• chr13-102124375-G-T
• rs9518638
• ENST00000376131.9:c.209-249079C>A

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-249079C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,932 control chromosomes in the GnomAD database, including 3,259 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 (3259 hom., cov: 32)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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: 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_175929.3	c.209-249079C>A		intron_variant	Intron 1 of 4		NP_787125.1
FGF14	NM_001321939.2	c.209-255547C>A		intron_variant	Intron 1 of 3		NP_001308868.1
FGF14	NM_001321945.2	c.92-249079C>A		intron_variant	Intron 2 of 5		NP_001308874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376131.9	c.209-249079C>A		intron_variant	Intron 1 of 4	1		ENSP00000365301.3
FGF14	ENST00000418923.3	c.92-249079C>A		intron_variant	Intron 2 of 5	3		ENSP00000516414.1
FGF14	ENST00000706494.1	c.-60+242070C>A		intron_variant	Intron 3 of 6			ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30507 AN: 151814 Hom.: 3256 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.201 AC: 30530 AN: 151932 Hom.: 3259 Cov.: 32 AF XY: 0.200 AC XY: 14848 AN XY: 74262

African (AFR) AF: 0.175 AC: 7276 AN: 41466

American (AMR) AF: 0.261 AC: 3972 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3462

East Asian (EAS) AF: 0.0660 AC: 342 AN: 5178

South Asian (SAS) AF: 0.203 AC: 977 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1622 AN: 10560

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

European-Non Finnish (NFE) AF: 0.220 AC: 14913 AN: 67886

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.211 Hom.: 971

Bravo AF: 0.208

Asia WGS AF: 0.130 AC: 451 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.39
PhyloP100		-1.0
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: rs9518638; hg19: chr13-102776725;