chr13-102060909-C-T

Variant names:

• chr13-102060909-C-T
• rs7992504
• ENST00000376131.9:c.209-185613G>A

Variant summary

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

The NM_175929.3(FGF14):​c.209-185613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,992 control chromosomes in the GnomAD database, including 11,921 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 0.39 (11921 hom., cov: 32)
• Consequence: FGF14 NM_175929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 5 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: Orphanet, Ambry Genetics
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175929.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	NM_175929.3		c.209-185613G>A		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.209-192081G>A		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.92-185613G>A		intron	N/A	NP_001308874.1	A0A9L9PXK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376131.9	TSL:1	c.209-185613G>A		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.92-185613G>A		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-59-185613G>A		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58771 AN: 151874 Hom.: 11911 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.387 AC: 58822 AN: 151992 Hom.: 11921 Cov.: 32 AF XY: 0.389 AC XY: 28931 AN XY: 74284

African (AFR) AF: 0.418 AC: 17341 AN: 41458

American (AMR) AF: 0.463 AC: 7075 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3545 AN: 5122

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3362 AN: 10576

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23043 AN: 67952

Other (OTH) AF: 0.390 AC: 823 AN: 2112

Alfa AF: 0.383 Hom.: 2170

Bravo AF: 0.397

Asia WGS AF: 0.526 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		0.29
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: rs7992504; hg19: chr13-102713259;