4-80292638-T-A

Variant names:

• chr4-80292638-T-A
• rs726896
• ENST00000507780.1:n.343-8645T>A

Variant summary

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

The ENST00000507780.1(FGF5):​n.343-8645T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,056 control chromosomes in the GnomAD database, including 28,657 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 0.59 (28657 hom., cov: 32)
• Consequence: FGF5 ENST00000507780.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• familial isolated trichomegaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• trichomegaly

  Inheritance: AR Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF5	ENST00000507780.1	n.343-8645T>A		intron_variant	Intron 2 of 4	3		ENSP00000423903.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89334 AN: 151938 Hom.: 28638 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.588 AC: 89388 AN: 152056 Hom.: 28657 Cov.: 32 AF XY: 0.589 AC XY: 43774 AN XY: 74334

African (AFR) AF: 0.316 AC: 13113 AN: 41500

American (AMR) AF: 0.636 AC: 9706 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1973 AN: 3464

East Asian (EAS) AF: 0.634 AC: 3281 AN: 5178

South Asian (SAS) AF: 0.519 AC: 2500 AN: 4814

European-Finnish (FIN) AF: 0.766 AC: 8104 AN: 10578

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48723 AN: 67936

Other (OTH) AF: 0.579 AC: 1225 AN: 2114

Alfa AF: 0.639 Hom.: 3929

Bravo AF: 0.566

Asia WGS AF: 0.549 AC: 1912 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.5
DANN	Benign	0.73
PhyloP100		-0.045

Splicing

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

Other links and lift over

dbSNP: rs726896; hg19: chr4-81213792;