5-133245995-C-T

Position:

• chr5-133245995-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL4	NM_015082.2	c.894+3415G>A		intron_variant		ENST00000265342.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL4	ENST00000265342.12	c.894+3415G>A		intron_variant		5	NM_015082.2	P1
	ENST00000515122.1	n.894-538C>T		intron_variant, non_coding_transcript_variant		2
	ENST00000504312.1	n.138-538C>T		intron_variant, non_coding_transcript_variant		4
FSTL4	ENST00000507112.1	n.305+3415G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.415

Alfa AF: 0.399 Hom.: 3111

Bravo AF: 0.474

Asia WGS AF: 0.529 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.77

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: rs17166444; hg19: chr5-132581687;