chr5-133712084-T-C

Position:

• chr5-133712084-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-10-108091A>G		intron_variant			XP_011541585.1
		n.133712084T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.806

Alfa AF: 0.778 Hom.: 63761

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6596147; hg19: chr5-133047775;