5-133568165-C-G

Variant names:

• chr5-133568165-C-G
• rs398606
• NM_015082.2:c.127-946G>C

Variant summary

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

The NM_015082.2(FSTL4):​c.127-946G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,842 control chromosomes in the GnomAD database, including 14,612 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 0.43 (14612 hom., cov: 31)
• Consequence: FSTL4 NM_015082.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	NM_015082.2	c.127-946G>C		intron_variant	Intron 2 of 15	ENST00000265342.12	NP_055897.1
FSTL4	XM_011543283.2	c.127-946G>C		intron_variant	Intron 2 of 15		XP_011541585.1
FSTL4	XM_011543284.3	c.127-946G>C		intron_variant	Intron 2 of 14		XP_011541586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12	c.127-946G>C		intron_variant	Intron 2 of 15	5	NM_015082.2	ENSP00000265342.7
FSTL4	ENST00000510685.1	c.133-946G>C		intron_variant	Intron 1 of 3	3		ENSP00000427662.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65639 AN: 151726 Hom.: 14576 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.433 AC: 65737 AN: 151842 Hom.: 14612 Cov.: 31 AF XY: 0.432 AC XY: 32061 AN XY: 74184

African (AFR) AF: 0.531 AC: 21972 AN: 41372

American (AMR) AF: 0.408 AC: 6225 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1330 AN: 5158

South Asian (SAS) AF: 0.398 AC: 1912 AN: 4808

European-Finnish (FIN) AF: 0.447 AC: 4700 AN: 10522

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26869 AN: 67934

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.262 Hom.: 610

Bravo AF: 0.434

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.36
PhyloP100		0.43
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: rs398606; hg19: chr5-132903856;