Variant 8-22042891-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_003867.4(FGF17):c.-38G>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 0.0113 in 1,611,858 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 17 hom., cov: 33)

Exomes 𝑓: 0.012 ( 107 hom. )

Consequence

FGF17
NM_003867.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.64

Variant links:

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]

FGF17 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 8-22042891-G-A is Benign according to our data. Variant chr8-22042891-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0116 (16895/1459540) while in subpopulation MID AF= 0.0326 (188/5766). AF 95% confidence interval is 0.0288. There are 107 homozygotes in gnomad4_exome. There are 8288 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1366 AD,Multigenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF17	NM_003867.4 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/5	ENST00000359441.4	NP_003858.1	O60258-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF17	ENST00000359441.4 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/5	1	NM_003867.4	ENSP00000352414.3		O60258-1
FGF17	ENST00000518533.5 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/5	1		ENSP00000431041.1		O60258-2

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1368

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00926

AC:

2274

AN:

245504

Hom.:

AF XY:

0.00949

AC XY:

1266

AN XY:

133374

show subpopulations

Gnomad AFR exome

AF:

0.00218

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00443

Gnomad FIN exome

AF:

0.00495

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0116

AC:

16895

AN:

1459540

Hom.:

107

Cov.:

AF XY:

0.0114

AC XY:

8288

AN XY:

726032

show subpopulations

Gnomad4 AFR exome

AF:

0.00419

Gnomad4 AMR exome

AF:

0.00706

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00897

AC:

1366

AN:

152318

Hom.:

Cov.:

AF XY:

0.00874

AC XY:

651

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00933

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

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

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