5-133293192-G-C

Variant names:

• chr5-133293192-G-C
• rs17166496
• NM_015082.2:c.727+19462C>G

Variant summary

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

The NM_015082.2(FSTL4):​c.727+19462C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,104 control chromosomes in the GnomAD database, including 21,650 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 0.53 (21650 hom., cov: 33)
• Consequence: FSTL4 NM_015082.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 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.727+19462C>G		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.727+19462C>G		intron	N/A	ENSP00000265342.7

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80052 AN: 151986 Hom.: 21653 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.526 AC: 80077 AN: 152104 Hom.: 21650 Cov.: 33 AF XY: 0.522 AC XY: 38834 AN XY: 74372

African (AFR) AF: 0.432 AC: 17914 AN: 41498

American (AMR) AF: 0.520 AC: 7956 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1434 AN: 5162

South Asian (SAS) AF: 0.438 AC: 2109 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5727 AN: 10580

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40905 AN: 67974

Other (OTH) AF: 0.565 AC: 1194 AN: 2114

Alfa AF: 0.545 Hom.: 2736

Bravo AF: 0.521

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.61
PhyloP100		0.24
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: rs17166496; hg19: chr5-132628884;