rs10491293

Variant names:

• chr5-133654206-C-G
• rs10491293
• XM_011543283.2:c.-10-50213G>C

Variant summary

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

The XM_011543283.2(FSTL4):​c.-10-50213G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,264 control chromosomes in the GnomAD database, including 1,212 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 (1212 hom., cov: 33)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-10-50213G>C		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: 0.121 AC: 18374 AN: 152146 Hom.: 1209 Cov.: 33

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.121 AC: 18374 AN: 152264 Hom.: 1212 Cov.: 33 AF XY: 0.124 AC XY: 9219 AN XY: 74438

African (AFR) AF: 0.0635 AC: 2639 AN: 41566

American (AMR) AF: 0.226 AC: 3454 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.169 AC: 874 AN: 5186

South Asian (SAS) AF: 0.112 AC: 539 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1638 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8463 AN: 68008

Other (OTH) AF: 0.135 AC: 286 AN: 2112

Alfa AF: 0.122 Hom.: 152

Bravo AF: 0.124

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.63
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs10491293; hg19: chr5-132989897;