rs11745088

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.76

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 719871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 649 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FST	NM_013409.3 link	c.454G>C	p.Glu152Gln	missense_variant	Exon 3 of 6	ENST00000256759.8	NP_037541.1	P19883-1A0A024QZU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FST	ENST00000256759.8 link	c.454G>C	p.Glu152Gln	missense_variant	Exon 3 of 6	1	NM_013409.3	ENSP00000256759.3	P19883-1
FST	ENST00000396947.7 link	c.454G>C	p.Glu152Gln	missense_variant	Exon 3 of 6	5		ENSP00000380151.2	P19883-2
FST	ENST00000504226.5 link	c.70G>C	p.Glu24Gln	missense_variant	Exon 1 of 4	3		ENSP00000426315.1	H0YA75
FST	ENST00000491717.1 link	n.555G>C		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.00440

AC:

1107

AN:

251438

AF XY:

0.00450

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 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

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00150

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00513

AC:

134

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000556

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0110

AC:

587

AN:

53420

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00633

AC:

7041

AN:

1111970

Other (OTH)

AF:

0.00517

AC:

312

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

430

860

1289

1719

2149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152306

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

304

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41568

American (AMR)

AF:

0.00209

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00634

AC:

431

AN:

68034

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

9.8

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

PromoterAI

0.059

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.40

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over