ENST00000376131.9:c.209-171415T>C

Variant names:

• chr13-102046711-A-G
• rs1542409
• ENST00000376131.9:c.209-171415T>C

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-171415T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,084 control chromosomes in the GnomAD database, including 17,654 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 0.47 (17654 hom., cov: 33)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_175929.3	c.209-171415T>C		intron_variant	Intron 1 of 4		NP_787125.1
FGF14	NM_001321939.2	c.209-177883T>C		intron_variant	Intron 1 of 3		NP_001308868.1
FGF14	NM_001321945.2	c.92-171415T>C		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.209-171415T>C		intron_variant	Intron 1 of 4	1		ENSP00000365301.3
FGF14	ENST00000418923.3	c.92-171415T>C		intron_variant	Intron 2 of 5	3		ENSP00000516414.1
FGF14	ENST00000706494.1	c.-59-171415T>C		intron_variant	Intron 3 of 6			ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71775 AN: 151966 Hom.: 17634 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.472 AC: 71838 AN: 152084 Hom.: 17654 Cov.: 33 AF XY: 0.471 AC XY: 35027 AN XY: 74334

African (AFR) AF: 0.567 AC: 23507 AN: 41484

American (AMR) AF: 0.544 AC: 8306 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3764 AN: 5182

South Asian (SAS) AF: 0.440 AC: 2122 AN: 4822

European-Finnish (FIN) AF: 0.338 AC: 3579 AN: 10578

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27573 AN: 67954

Other (OTH) AF: 0.487 AC: 1027 AN: 2108

Alfa AF: 0.428 Hom.: 8856

Bravo AF: 0.492

Asia WGS AF: 0.548 AC: 1903 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		1.6
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: rs1542409; hg19: chr13-102699061;