Variant 4-80275012-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP3PP5

The NM_004464.4(FGF5):c.459+1delG variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,245,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

FGF5
NM_004464.4 splice_donor, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.14

Variant links:

Genes affected

FGF5 (HGNC:3683): (fibroblast growth factor 5) 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. This gene was identified as an oncogene, which confers transforming potential when transfected into mammalian cells. Targeted disruption of the homolog of this gene in mouse resulted in the phenotype of abnormally long hair, which suggested a function as an inhibitor of hair elongation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FGF5 links:

FGF5 (HGNC:):

FGF5 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 2: max_spliceai, phyloP100way_vertebrate [when was below the threshold]

PP5

Variant 4-80275012-TG-T is Pathogenic according to our data. Variant chr4-80275012-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 141410.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-80275012-TG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FGF5	NM_004464.4 linkuse as main transcript	c.459+1delG	splice_donor_variant, intron_variant	ENST00000312465.12	NP_004455.2	P12034-1Q8NBG6A0A7U3L5M4
FGF5	NM_001291812.2 linkuse as main transcript	c.30+1delG	splice_donor_variant, intron_variant		NP_001278741.1	Q8NBG6
FGF5	NM_033143.2 linkuse as main transcript	c.355+7834delG	intron_variant		NP_149134.1	P12034-2Q8NBG6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FGF5	ENST00000312465.12 linkuse as main transcript	c.459+1delG	splice_donor_variant, intron_variant	1	NM_004464.4	ENSP00000311697.7	P12034-1
FGF5	ENST00000456523.3 linkuse as main transcript	c.355+7834delG	intron_variant	1		ENSP00000398353.3	P12034-2
FGF5	ENST00000503413.1 linkuse as main transcript	n.408+1delG	splice_donor_variant, intron_variant	2
FGF5	ENST00000507780.1 linkuse as main transcript	n.342+1delG	splice_donor_variant, intron_variant	3		ENSP00000423903.1	H0Y9E2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000429

AC:

AN:

232842

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1245898

Hom.:

Cov.:

AF XY:

0.00000794

AC XY:

AN XY:

629568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000774

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Trichomegaly

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 22, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.58

Position offset: -2

DS_DL_spliceai

0.99

Position offset: 0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over