8-22043246-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003867.4(FGF17):c.72+65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,533,786 control chromosomes in the GnomAD database, including 117,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14889 hom., cov: 33)
  • Exomes 𝑓: 0.38 (102670 hom.)
• Consequence: FGF17 NM_003867.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-22043246-A-G is Benign according to our data. Variant chr8-22043246-A-G is described in ClinVar as [Benign]. Clinvar id is 1248234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF17	NM_003867.4	c.72+65A>G		intron_variant		ENST00000359441.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF17	ENST00000359441.4	c.72+65A>G		intron_variant		1	NM_003867.4	P4
FGF17	ENST00000518533.5	c.72+65A>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65339 AN: 151850 Hom.: 14847 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.382 AC: 527591 AN: 1381816 Hom.: 102670 AF XY: 0.382 AC XY: 263445 AN XY: 690350

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.431 AC: 65436 AN: 151970 Hom.: 14889 Cov.: 33 AF XY: 0.430 AC XY: 31925 AN XY: 74288

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.412

Alfa AF: 0.382 Hom.: 2225

Bravo AF: 0.431

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.0
Dann	Benign	0.57

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: rs900779; hg19: chr8-21900757; COSMIC: COSV63925538; COSMIC: COSV63925538;