Variant rs11745088 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013409.3(FST):c.454G>C(p.Glu152Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,614,152 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 32 hom. )

Consequence

FST
NM_013409.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.76

Variant links:

Genes affected

FST (HGNC:3971): (follistatin) Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. [provided by RefSeq, Jul 2008]

FST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072375834).

BP6

Variant 5-53483680-G-C is Benign according to our data. Variant chr5-53483680-G-C is described in ClinVar as [Benign]. Clinvar id is 719871.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 650 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FST	NM_013409.3 linkuse as main transcript	c.454G>C	p.Glu152Gln	missense_variant	3/6	ENST00000256759.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FST	ENST00000256759.8 linkuse as main transcript	c.454G>C	p.Glu152Gln	missense_variant	3/6	1	NM_013409.3	A1	P19883-1
FST	ENST00000396947.7 linkuse as main transcript	c.454G>C	p.Glu152Gln	missense_variant	3/6	5		P4	P19883-2
FST	ENST00000504226.5 linkuse as main transcript	c.70G>C	p.Glu24Gln	missense_variant	1/4	3
FST	ENST00000491717.1 linkuse as main transcript	n.555G>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00427

AC:

650

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00633

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00440

AC:

1107

AN:

251438

Hom.:

AF XY:

0.00450

AC XY:

612

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00648

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00564

AC:

8242

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00545

AC XY:

3965

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00513

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.00633

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152306

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

304

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.00634

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00533

Hom.:

Bravo

AF:

0.00368

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00443

AC:

538

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.;T

Eigen

Benign

0.049

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.47

N;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.35

B;.;.

Vest4

0.29

MVP

0.51

MPC

1.1

ClinPred

0.058

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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