rs17166444

Variant names:

• chr5-133245995-C-T
• rs17166444
• NM_015082.2:c.894+3415G>A

Variant summary

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

The NM_015082.2(FSTL4):​c.894+3415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,068 control chromosomes in the GnomAD database, including 19,098 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 0.44 (19098 hom., cov: 33)
• Consequence: FSTL4 NM_015082.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 4 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]

ENSG00000249478 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015082.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL4	NM_015082.2	MANE Select	c.894+3415G>A		intron	N/A	NP_055897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL4	ENST00000265342.12	TSL:5 MANE Select	c.894+3415G>A		intron	N/A	ENSP00000265342.7
	ENSG00000249478	ENST00000504312.1	TSL:4	n.138-538C>T		intron	N/A
	FSTL4	ENST00000507112.1	TSL:3	n.305+3415G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66153 AN: 151950 Hom.: 19047 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.436 AC: 66258 AN: 152068 Hom.: 19098 Cov.: 33 AF XY: 0.439 AC XY: 32592 AN XY: 74318

African (AFR) AF: 0.800 AC: 33192 AN: 41494

American (AMR) AF: 0.464 AC: 7085 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3466

East Asian (EAS) AF: 0.636 AC: 3285 AN: 5166

South Asian (SAS) AF: 0.376 AC: 1808 AN: 4810

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16048 AN: 67972

Other (OTH) AF: 0.415 AC: 874 AN: 2104

Alfa AF: 0.386 Hom.: 5314

Bravo AF: 0.474

Asia WGS AF: 0.529 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17166444; hg19: chr5-132581687;