rs12152850

Positions:

• chr5-53484523-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000256759.8(FST):​c.721+230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,144 control chromosomes in the GnomAD database, including 1,356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1356 hom., cov: 33)
• Consequence: FST ENST00000256759.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FST	NM_013409.3	c.721+230C>T		intron_variant		ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.721+230C>T		intron_variant		1	NM_013409.3	ENSP00000256759	A1
FST	ENST00000396947.7	c.721+230C>T		intron_variant		5		ENSP00000380151	P4
FST	ENST00000497789.2	c.78+230C>T		intron_variant		2		ENSP00000426971
FST	ENST00000504226.5	c.337+230C>T		intron_variant		3		ENSP00000426315

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18081 AN: 152028 Hom.: 1358 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18072 AN: 152144 Hom.: 1356 Cov.: 33 AF XY: 0.116 AC XY: 8612 AN XY: 74370

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.0755

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.130

Alfa AF: 0.144 Hom.: 219

Bravo AF: 0.113

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.6
DANN	Benign	0.82

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: rs12152850; hg19: chr5-52780353;