rs9327668

Variant names:

• chr5-133731114-C-T
• rs9327668
• XM_011543283.2:c.-11+110838G>A

Variant summary

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

The XM_011543283.2(FSTL4):​c.-11+110838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,998 control chromosomes in the GnomAD database, including 1,767 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 0.13 (1767 hom., cov: 31)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 2 publications found

Genes affected

FSTL4 (HGNC:21389): (follistatin like 4) Predicted to enable brain-derived neurotrophic factor binding activity and calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to act upstream of or within negative regulation of brain-derived neurotrophic factor receptor signaling pathway; negative regulation of collateral sprouting; and negative regulation of dendritic spine development. Predicted to be located in extracellular region and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-11+110838G>A		intron_variant	Intron 1 of 15		XP_011541585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19292 AN: 151880 Hom.: 1750 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.127 AC: 19350 AN: 151998 Hom.: 1767 Cov.: 31 AF XY: 0.126 AC XY: 9324 AN XY: 74286

African (AFR) AF: 0.248 AC: 10274 AN: 41410

American (AMR) AF: 0.0943 AC: 1441 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3466

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5170

South Asian (SAS) AF: 0.0433 AC: 208 AN: 4800

European-Finnish (FIN) AF: 0.0687 AC: 727 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5706 AN: 67974

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.0957 Hom.: 675

Bravo AF: 0.137

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.077
DANN	Benign	0.58
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9327668; hg19: chr5-133066805;