5-53481826-G-T

Variant names:

• chr5-53481826-G-T
• rs3797297
• NM_013409.3:c.85+950G>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.85+950G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,172 control chromosomes in the GnomAD database, including 2,534 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 0.18 (2534 hom., cov: 32)
• Consequence: FST NM_013409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 12 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FST	NM_013409.3	c.85+950G>T		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.85+950G>T		intron_variant	Intron 1 of 5	1	NM_013409.3	ENSP00000256759.3
FST	ENST00000396947.7	c.85+950G>T		intron_variant	Intron 1 of 5	5		ENSP00000380151.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27131 AN: 152054 Hom.: 2534 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.178 AC: 27133 AN: 152172 Hom.: 2534 Cov.: 32 AF XY: 0.179 AC XY: 13281 AN XY: 74386

African (AFR) AF: 0.128 AC: 5323 AN: 41532

American (AMR) AF: 0.199 AC: 3039 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3470

East Asian (EAS) AF: 0.157 AC: 810 AN: 5172

South Asian (SAS) AF: 0.146 AC: 704 AN: 4826

European-Finnish (FIN) AF: 0.201 AC: 2120 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13533 AN: 67990

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.189 Hom.: 331

Bravo AF: 0.177

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		1.8
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: rs3797297; hg19: chr5-52777656;