8-22042640-T-A

Position:

• chr8-22042640-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000518533.5(FGF17):​c.-289T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 592,130 control chromosomes in the GnomAD database, including 2,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (693 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1941 hom.)
• Consequence: FGF17 ENST00000518533.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303

Genes affected

FGF17 (HGNC:3673): (fibroblast growth factor 17) This gene encodes a member of the fibroblast growth factor (FGF) family. Member of the FGF family 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 protein is expressed during embryogenesis and in the adult cerebellum and cortex and may be essential for vascular growth and normal brain development. Mutations in this gene are the cause of hypogonadotropic hypogonadism 20 with or without anosmia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 8-22042640-T-A is Benign according to our data. Variant chr8-22042640-T-A is described in ClinVar as [Benign]. Clinvar id is 1244789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF17	XM_011544683.2	c.94-515T>A		intron_variant			XP_011542985.1
FGF17	XM_011544684.2	c.94-515T>A		intron_variant			XP_011542986.1
FGF17	XM_011544685.2	c.94-515T>A		intron_variant			XP_011542987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF17	ENST00000518533.5	c.-289T>A		5_prime_UTR_variant	1/5	1		ENSP00000431041.1

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8153 AN: 152144 Hom.: 693 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00683

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0374 AC: 16469 AN: 439868 Hom.: 1941 Cov.: 0 AF XY: 0.0357 AC XY: 8277 AN XY: 231814

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.00563

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.0188

Gnomad4 FIN exome AF: 0.00917

Gnomad4 NFE exome AF: 0.00685

Gnomad4 OTH exome AF: 0.0461

GnomAD4 genome AF: 0.0536 AC: 8164 AN: 152262 Hom.: 693 Cov.: 33 AF XY: 0.0552 AC XY: 4112 AN XY: 74452

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0585

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.0252

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.00684

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0339 Hom.: 32

Bravo AF: 0.0631

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.9
DANN	Benign	0.90

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: rs3176263; hg19: chr8-21900151;