rs6596140

Variant names:

• chr5-133686160-C-T
• rs6596140
• XM_011543283.2:c.-10-82167G>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.-10-82167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,098 control chromosomes in the GnomAD database, including 9,057 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 0.34 (9057 hom., cov: 33)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-10-82167G>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: 0.343 AC: 52095 AN: 151980 Hom.: 9045 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.343 AC: 52143 AN: 152098 Hom.: 9057 Cov.: 33 AF XY: 0.343 AC XY: 25527 AN XY: 74346

African (AFR) AF: 0.340 AC: 14094 AN: 41482

American (AMR) AF: 0.369 AC: 5640 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1556 AN: 5166

South Asian (SAS) AF: 0.380 AC: 1832 AN: 4818

European-Finnish (FIN) AF: 0.351 AC: 3708 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23238 AN: 67984

Other (OTH) AF: 0.327 AC: 691 AN: 2114

Alfa AF: 0.339 Hom.: 29588

Bravo AF: 0.343

Asia WGS AF: 0.372 AC: 1297 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	3.2
DANN	Benign	0.47
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs6596140; hg19: chr5-133021851;