13-102056115-G-A

Variant names:

• chr13-102056115-G-A
• rs4772439
• ENST00000376131.9:c.209-180819C>T

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-180819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,022 control chromosomes in the GnomAD database, including 8,946 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 0.33 (8946 hom., cov: 32)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_175929.3	c.209-180819C>T		intron_variant	Intron 1 of 4		NP_787125.1
FGF14	NM_001321939.2	c.209-187287C>T		intron_variant	Intron 1 of 3		NP_001308868.1
FGF14	NM_001321945.2	c.92-180819C>T		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.209-180819C>T		intron_variant	Intron 1 of 4	1		ENSP00000365301.3
FGF14	ENST00000418923.3	c.92-180819C>T		intron_variant	Intron 2 of 5	3		ENSP00000516414.1
FGF14	ENST00000706494.1	c.-59-180819C>T		intron_variant	Intron 3 of 6			ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50478 AN: 151904 Hom.: 8946 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.332 AC: 50484 AN: 152022 Hom.: 8946 Cov.: 32 AF XY: 0.335 AC XY: 24905 AN XY: 74320

African (AFR) AF: 0.276 AC: 11447 AN: 41472

American (AMR) AF: 0.442 AC: 6753 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3321 AN: 5166

South Asian (SAS) AF: 0.391 AC: 1882 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2771 AN: 10560

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22005 AN: 67950

Other (OTH) AF: 0.346 AC: 728 AN: 2106

Alfa AF: 0.325 Hom.: 24448

Bravo AF: 0.341

Asia WGS AF: 0.484 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.22
PhyloP100		-1.8
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: rs4772439; hg19: chr13-102708465;