Variant 13-21701807-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002010.3(FGF9):c.*372A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 275,282 control chromosomes in the GnomAD database, including 5,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3933 hom., cov: 31)

Exomes 𝑓: 0.12 ( 1176 hom. )

Consequence

FGF9
NM_002010.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

FGF9 (HGNC:3687): (fibroblast growth factor 9) 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 protein was isolated as a secreted factor that exhibits a growth-stimulating effect on cultured glial cells. In nervous system, this protein is produced mainly by neurons and may be important for glial cell development. Expression of the mouse homolog of this gene was found to be dependent on Sonic hedgehog (Shh) signaling. Mice lacking the homolog gene displayed a male-to-female sex reversal phenotype, which suggested a role in testicular embryogenesis. [provided by RefSeq, Jul 2008]

FGF9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-21701807-A-T is Benign according to our data. Variant chr13-21701807-A-T is described in ClinVar as [Benign]. Clinvar id is 311441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF9	NM_002010.3 linkuse as main transcript	c.*372A>T		3_prime_UTR_variant	3/3	ENST00000382353.6
FGF9	XM_011534996.3 linkuse as main transcript	c.*372A>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF9	ENST00000382353.6 linkuse as main transcript	c.*372A>T		3_prime_UTR_variant	3/3	1	NM_002010.3	P1
FGF9	ENST00000478546.1 linkuse as main transcript	n.759A>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29352

AN:

151362

Hom.:

3911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0339

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.119

AC:

14731

AN:

123804

Hom.:

1176

Cov.:

AF XY:

0.114

AC XY:

7509

AN XY:

65706

show subpopulations

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.0687

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0333

Gnomad4 SAS exome

AF:

0.0827

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.194

AC:

29433

AN:

151478

Hom.:

3933

Cov.:

AF XY:

0.191

AC XY:

14117

AN XY:

74002

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.0836

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.133

Hom.:

912

Bravo

AF:

0.199

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple synostoses syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

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

-0.54

CADD

Benign

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

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