5-53482380-G-A

Variant names:

• chr5-53482380-G-A
• rs3756498
• NM_013409.3:c.86-500G>A

Variant summary

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

The NM_013409.3(FST):​c.86-500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 133,418 control chromosomes in the GnomAD database, including 2,392 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 0.20 (2392 hom., cov: 28)
• Consequence: FST NM_013409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 10 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]

ENSG00000306075 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FST	NM_013409.3	c.86-500G>A		intron_variant	Intron 1 of 5	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.86-500G>A		intron_variant	Intron 1 of 5	1	NM_013409.3	ENSP00000256759.3
FST	ENST00000396947.7	c.86-500G>A		intron_variant	Intron 1 of 5	5		ENSP00000380151.2
ENSG00000306075	ENST00000815109.1	n.*82C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.196 AC: 26200 AN: 133346 Hom.: 2392 Cov.: 28

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.196 AC: 26204 AN: 133418 Hom.: 2392 Cov.: 28 AF XY: 0.200 AC XY: 12774 AN XY: 63790

African (AFR) AF: 0.150 AC: 5160 AN: 34442

American (AMR) AF: 0.237 AC: 2908 AN: 12294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 798 AN: 3384

East Asian (EAS) AF: 0.171 AC: 786 AN: 4592

South Asian (SAS) AF: 0.147 AC: 623 AN: 4246

European-Finnish (FIN) AF: 0.263 AC: 1995 AN: 7580

Middle Eastern (MID) AF: 0.342 AC: 80 AN: 234

European-Non Finnish (NFE) AF: 0.206 AC: 13195 AN: 63960

Other (OTH) AF: 0.214 AC: 388 AN: 1812

Alfa AF: 0.186 Hom.: 8683

Bravo AF: 0.174

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		-0.0020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3756498; hg19: chr5-52778210; COSMIC: COSV56816815; COSMIC: COSV56816815;