5-133293192-G-C

Position:

• chr5-133293192-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSTL4	NM_015082.2	c.727+19462C>G		intron_variant		ENST00000265342.12	NP_055897.1
FSTL4	XM_011543283.2	c.727+19462C>G		intron_variant			XP_011541585.1
FSTL4	XM_011543284.3	c.727+19462C>G		intron_variant			XP_011541586.1
FSTL4	XM_011543286.4	c.304+19462C>G		intron_variant			XP_011541588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12	c.727+19462C>G		intron_variant		5	NM_015082.2	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

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.565

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs17166496; hg19: chr5-132628884;