rs12152850

Variant names:

• chr5-53484523-C-T
• rs12152850
• NM_013409.3:c.721+230C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013409.3(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 NM_013409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FST	NM_013409.3	c.721+230C>T		intron_variant	Intron 4 of 5	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.721+230C>T		intron_variant	Intron 4 of 5	1	NM_013409.3	ENSP00000256759.3
FST	ENST00000396947.7	c.721+230C>T		intron_variant	Intron 4 of 5	5		ENSP00000380151.2
FST	ENST00000504226.5	c.337+230C>T		intron_variant	Intron 2 of 3	3		ENSP00000426315.1
FST	ENST00000497789.2	c.76+230C>T		intron_variant	Intron 1 of 2	2		ENSP00000426971.1

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

African (AFR) AF: 0.0369 AC: 1531 AN: 41514

American (AMR) AF: 0.111 AC: 1699 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5180

South Asian (SAS) AF: 0.0755 AC: 364 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10570

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11602 AN: 67990

Other (OTH) AF: 0.130 AC: 274 AN: 2110

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
PhyloP100		-0.018
PromoterAI		-0.0064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12152850; hg19: chr5-52780353;