13-101847189-T-G

Variant names:

• chr13-101847189-T-G
• rs2984842
• NM_004115.4:c.408+21536A>C

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+21536A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,782 control chromosomes in the GnomAD database, including 28,500 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 0.61 (28500 hom., cov: 32)
• Consequence: FGF14 NM_004115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_004115.4	c.408+21536A>C		intron_variant	Intron 3 of 4	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143.5	c.408+21536A>C		intron_variant	Intron 3 of 4	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92017 AN: 151664 Hom.: 28466 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.607 AC: 92099 AN: 151782 Hom.: 28500 Cov.: 32 AF XY: 0.610 AC XY: 45238 AN XY: 74130

African (AFR) AF: 0.719 AC: 29789 AN: 41448

American (AMR) AF: 0.616 AC: 9371 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1970 AN: 3464

East Asian (EAS) AF: 0.753 AC: 3864 AN: 5132

South Asian (SAS) AF: 0.698 AC: 3360 AN: 4814

European-Finnish (FIN) AF: 0.550 AC: 5796 AN: 10530

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35998 AN: 67866

Other (OTH) AF: 0.596 AC: 1255 AN: 2106

Alfa AF: 0.566 Hom.: 47571

Bravo AF: 0.614

Asia WGS AF: 0.734 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2984842; hg19: chr13-102499539;