4-80286809-A-G

Position:

• chr4-80286809-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004464.4(FGF5):​c.*137A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 657,840 control chromosomes in the GnomAD database, including 38,008 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 0.34 (8838 hom., cov: 32)
  • Exomes 𝑓: 0.34 (29170 hom.)
• Consequence: FGF5 NM_004464.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF5	NM_004464.4	c.*137A>G		3_prime_UTR_variant	3/3	ENST00000312465.12	NP_004455.2
FGF5	NM_001291812.2	c.*137A>G		3_prime_UTR_variant	3/3		NP_001278741.1
FGF5	NM_033143.2	c.*468A>G		3_prime_UTR_variant	2/2		NP_149134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF5	ENST00000312465.12	c.*137A>G		3_prime_UTR_variant	3/3	1	NM_004464.4	ENSP00000311697	P1
FGF5	ENST00000456523.3	c.*468A>G		3_prime_UTR_variant	2/2	1		ENSP00000398353
FGF5	ENST00000503413.1	n.893A>G		non_coding_transcript_exon_variant	3/3	2
FGF5	ENST00000507780.1	c.342+11797A>G		intron_variant, NMD_transcript_variant		3		ENSP00000423903

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51531 AN: 151930 Hom.: 8835 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.336 AC: 169947 AN: 505792 Hom.: 29170 Cov.: 6 AF XY: 0.332 AC XY: 87367 AN XY: 263438

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.339 AC: 51544 AN: 152048 Hom.: 8838 Cov.: 32 AF XY: 0.336 AC XY: 24971 AN XY: 74320

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.320

Alfa AF: 0.349 Hom.: 12337

Bravo AF: 0.343

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs3733336; hg19: chr4-81207963;