rs769509086

Variant names:

• chr5-133199153-C-A
• NM_015082.2:c.2471G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-133199153-C-A
• chr5-133199153-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015082.2(FSTL4):​c.2471G>T​(p.Arg824Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,449,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FSTL4 NM_015082.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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]

ENSG00000248245 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23768121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	NM_015082.2	c.2471G>T	p.Arg824Leu	missense_variant	Exon 16 of 16	ENST00000265342.12	NP_055897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12	c.2471G>T	p.Arg824Leu	missense_variant	Exon 16 of 16	5	NM_015082.2	ENSP00000265342.7
FSTL4	ENST00000509525.5	n.1689G>T		non_coding_transcript_exon_variant	Exon 8 of 8	2
ENSG00000248245	ENST00000509051.1	n.76-8683C>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1449076 Hom.: 0 Cov.: 31 AF XY: 0.00000696 AC XY: 5 AN XY: 718836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000710

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.9	D;.
REVEL	Benign	0.15
Sift	Benign	0.037	D;.
Sift4G	Benign	0.10	T;D
Polyphen		0.45	B;.
Vest4		0.43
MutPred		0.46		Loss of MoRF binding (P = 0.0577);.;
MVP		0.38
MPC		0.43
ClinPred		0.40	T
GERP RS		-0.97
Varity_R		0.16
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-132534845; COSMIC: COSV99532281; COSMIC: COSV99532281;