NM_004115.4:c.408+48823A>G

Variant names:

• chr13-101819902-T-C
• rs10508076
• NM_004115.4:c.408+48823A>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+48823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,106 control chromosomes in the GnomAD database, including 3,718 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 0.21 (3718 hom., cov: 32)
• Consequence: FGF14 NM_004115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004115.4. 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_004115.4	MANE Select	c.408+48823A>G		intron	N/A	NP_004106.1
	FGF14	NM_175929.3		c.423+48823A>G		intron	N/A	NP_787125.1
	FGF14	NM_001321939.2		c.312+48823A>G		intron	N/A	NP_001308868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376143.5	TSL:1 MANE Select	c.408+48823A>G		intron	N/A	ENSP00000365313.4
	FGF14	ENST00000376131.9	TSL:1	c.423+48823A>G		intron	N/A	ENSP00000365301.3
	FGF14	ENST00000418923.3	TSL:3	c.306+48823A>G		intron	N/A	ENSP00000516414.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32618 AN: 151988 Hom.: 3712 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.215 AC: 32658 AN: 152106 Hom.: 3718 Cov.: 32 AF XY: 0.214 AC XY: 15922 AN XY: 74334

African (AFR) AF: 0.238 AC: 9874 AN: 41472

American (AMR) AF: 0.241 AC: 3691 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5180

South Asian (SAS) AF: 0.106 AC: 512 AN: 4824

European-Finnish (FIN) AF: 0.254 AC: 2683 AN: 10576

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14340 AN: 67974

Other (OTH) AF: 0.198 AC: 419 AN: 2114

Alfa AF: 0.214 Hom.: 2126

Bravo AF: 0.217

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10508076; hg19: chr13-102472252;