chr5-133686249-A-G

Variant names:

• chr5-133686249-A-G
• rs6596142
• XM_011543283.2:c.-10-82256T>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.-10-82256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,942 control chromosomes in the GnomAD database, including 10,133 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 0.36 (10133 hom., cov: 33)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55302 AN: 151822 Hom.: 10120 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.364 AC: 55350 AN: 151942 Hom.: 10133 Cov.: 33 AF XY: 0.365 AC XY: 27104 AN XY: 74260

African (AFR) AF: 0.356 AC: 14743 AN: 41462

American (AMR) AF: 0.392 AC: 5988 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3468

East Asian (EAS) AF: 0.337 AC: 1739 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1909 AN: 4806

European-Finnish (FIN) AF: 0.376 AC: 3964 AN: 10544

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24644 AN: 67900

Other (OTH) AF: 0.365 AC: 772 AN: 2116

Alfa AF: 0.364 Hom.: 32200

Bravo AF: 0.366

Asia WGS AF: 0.396 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		0.070

Splicing

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

Other links and lift over

dbSNP: rs6596142; hg19: chr5-133021940;