dbSNP rs544434: FGF14:c.208+204556A>G (chr13-102196915-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000376131.9(FGF14):c.208+204556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 151,842 control chromosomes in the GnomAD database, including 1,628 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 0.080 ( 1628 hom., cov: 32)

Consequence

FGF14
ENST00000376131.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.358

Publications

1 publications found

Variant links:

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

FGF14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
FGF14	NM_175929.3 link	c.208+204556A>G	intron_variant	Intron 1 of 4	NP_787125.1	Q92915-2
FGF14	NM_001321939.2 link	c.208+204556A>G	intron_variant	Intron 1 of 3	NP_001308868.1
FGF14	NM_001321945.2 link	c.91+204556A>G	intron_variant	Intron 2 of 5	NP_001308874.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
FGF14	ENST00000376131.9 link	c.208+204556A>G	intron_variant	Intron 1 of 4	1	ENSP00000365301.3	Q92915-2
FGF14	ENST00000418923.3 link	c.91+204556A>G	intron_variant	Intron 2 of 5	3	ENSP00000516414.1	A0A9L9PXK7
FGF14	ENST00000706494.1 link	c.-60+169530A>G	intron_variant	Intron 3 of 6		ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12069

AN:

151732

Hom.:

1623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0532

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

GnomAD4 genome

AF:

0.0797

AC:

12106

AN:

151842

Hom.:

1628

Cov.:

AF XY:

0.0765

AC XY:

5678

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.276

AC:

11402

AN:

41268

American (AMR)

AF:

0.0297

AC:

454

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000416

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

67998

Other (OTH)

AF:

0.0527

AC:

111

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

420

839

1259

1678

2098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0500

Hom.:

282

Bravo

AF:

0.0916

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

(source)

DANN

Benign

0.74

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over