5-133712084-T-C

Variant names:

• chr5-133712084-T-C
• rs6596147
• XM_011543283.2:c.-10-108091A>G

Variant summary

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

The XM_011543283.2(FSTL4):​c.-10-108091A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,164 control chromosomes in the GnomAD database, including 53,508 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 0.83 (53508 hom., cov: 31)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-10-108091A>G		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: 0.835 AC: 126887 AN: 152046 Hom.: 53448 Cov.: 31

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.835 AC: 127005 AN: 152164 Hom.: 53508 Cov.: 31 AF XY: 0.836 AC XY: 62184 AN XY: 74398

African (AFR) AF: 0.956 AC: 39694 AN: 41534

American (AMR) AF: 0.835 AC: 12767 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4745 AN: 5172

South Asian (SAS) AF: 0.776 AC: 3737 AN: 4816

European-Finnish (FIN) AF: 0.828 AC: 8747 AN: 10570

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52243 AN: 68002

Other (OTH) AF: 0.806 AC: 1696 AN: 2104

Alfa AF: 0.784 Hom.: 81119

Bravo AF: 0.841

Asia WGS AF: 0.871 AC: 3029 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.041
DANN	Benign	0.54
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs6596147; hg19: chr5-133047775;