rs755270499

Variant names:

• chr5-133199129-C-A
• rs755270499
• NM_015082.2:c.2495G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-133199129-C-A
• chr5-133199129-C-G
• chr5-133199129-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015082.2(FSTL4):​c.2495G>T​(p.Gly832Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,568,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G832R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FSTL4 NM_015082.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 0 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]

ENSG00000248245 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08285591).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL4	NM_015082.2	MANE Select	c.2495G>T	p.Gly832Val	missense	Exon 16 of 16	NP_055897.1	Q6MZW2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL4	ENST00000265342.12	TSL:5 MANE Select	c.2495G>T	p.Gly832Val	missense	Exon 16 of 16	ENSP00000265342.7	Q6MZW2-1
	FSTL4	ENST00000897474.1		c.2597G>T	p.Gly866Val	missense	Exon 15 of 15	ENSP00000567533.1
	FSTL4	ENST00000897473.1		c.2468G>T	p.Gly823Val	missense	Exon 15 of 15	ENSP00000567532.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000452 AC: 1 AN: 221032 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416036 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697550

African (AFR) AF: 0.00 AC: 0 AN: 32734

American (AMR) AF: 0.00 AC: 0 AN: 41960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39204

South Asian (SAS) AF: 0.00 AC: 0 AN: 78320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4896

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085760

Other (OTH) AF: 0.00 AC: 0 AN: 58352

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.086
Sift	Benign	0.086	T
Sift4G	Benign	0.085	T
Polyphen		0.11	B
Vest4		0.12
MutPred		0.31		Gain of methylation at K831 (P = 0.0377)
MVP		0.23
MPC		0.39
ClinPred		0.12	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.58
Mutation Taster		=96/4	polymorphism

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: rs755270499; hg19: chr5-132534821;