chr13-101900898-G-T

Variant names:

• chr13-101900898-G-T
• rs9557754
• NM_004115.4:c.193+15555C>A

Variant summary

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

The NM_004115.4(FGF14):​c.193+15555C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,990 control chromosomes in the GnomAD database, including 7,082 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 0.30 (7082 hom., cov: 32)
• Consequence: FGF14 NM_004115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_004115.4	c.193+15555C>A		intron_variant	Intron 1 of 4	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143.5	c.193+15555C>A		intron_variant	Intron 1 of 4	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45059 AN: 151874 Hom.: 7071 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.297 AC: 45096 AN: 151990 Hom.: 7082 Cov.: 32 AF XY: 0.295 AC XY: 21943 AN XY: 74312

African (AFR) AF: 0.346 AC: 14320 AN: 41436

American (AMR) AF: 0.392 AC: 5987 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2310 AN: 5170

South Asian (SAS) AF: 0.224 AC: 1080 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2388 AN: 10554

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17047 AN: 67968

Other (OTH) AF: 0.292 AC: 616 AN: 2112

Alfa AF: 0.271 Hom.: 734

Bravo AF: 0.317

Asia WGS AF: 0.342 AC: 1187 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		0.71
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: rs9557754; hg19: chr13-102553248;