rs11617740

Variant names:

• chr13-102027776-G-A
• rs11617740
• ENST00000376131.9:c.209-152480C>T

Variant summary

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

The ENST00000376131.9(FGF14):​c.209-152480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 152,040 control chromosomes in the GnomAD database, including 304 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 0.056 (304 hom., cov: 32)
• Consequence: FGF14 ENST00000376131.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_175929.3	c.209-152480C>T		intron_variant	Intron 1 of 4		NP_787125.1
FGF14	NM_001321939.2	c.209-158948C>T		intron_variant	Intron 1 of 3		NP_001308868.1
FGF14	NM_001321945.2	c.92-152480C>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.209-152480C>T		intron_variant	Intron 1 of 4	1		ENSP00000365301.3
FGF14	ENST00000418923.3	c.92-152480C>T		intron_variant	Intron 2 of 5	3		ENSP00000516414.1
FGF14	ENST00000706494.1	c.-59-152480C>T		intron_variant	Intron 3 of 6			ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8484 AN: 151922 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0558 AC: 8481 AN: 152040 Hom.: 304 Cov.: 32 AF XY: 0.0522 AC XY: 3880 AN XY: 74312

African (AFR) AF: 0.0158 AC: 658 AN: 41524

American (AMR) AF: 0.0613 AC: 934 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4824

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5846 AN: 67926

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0734 Hom.: 912

Bravo AF: 0.0561

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		0.43
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: rs11617740; hg19: chr13-102680126;