chr5-53484756-T-C

Position:

• chr5-53484756-T-C

Variant summary

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

The NM_013409.3(FST):​c.722-241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,240 control chromosomes in the GnomAD database, including 1,436 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 (1436 hom., cov: 32)
• Consequence: FST NM_013409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FST	NM_013409.3	c.722-241T>C		intron_variant		ENST00000256759.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FST	ENST00000256759.8	c.722-241T>C		intron_variant		1	NM_013409.3	A1
FST	ENST00000396947.7	c.722-241T>C		intron_variant		5		P4
FST	ENST00000497789.2	c.79-244T>C		intron_variant		2
FST	ENST00000504226.5	c.338-244T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18514 AN: 152122 Hom.: 1438 Cov.: 32

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.122 AC: 18505 AN: 152240 Hom.: 1436 Cov.: 32 AF XY: 0.119 AC XY: 8867 AN XY: 74438

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.133

Alfa AF: 0.149 Hom.: 240

Bravo AF: 0.114

Asia WGS AF: 0.0540 AC: 190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.35
DANN	Benign	0.45

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: rs12153205; hg19: chr5-52780586;