Variant 5-133201952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015082.2(FSTL4):c.1807C>T(p.Leu603Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00028 in 1,605,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

FSTL4
NM_015082.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.12

Variant links:

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]

FSTL4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012827098).

BP6

Variant 5-133201952-G-A is Benign according to our data. Variant chr5-133201952-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787042.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL4	NM_015082.2 linkuse as main transcript	c.1807C>T	p.Leu603Phe	missense_variant	15/16	ENST00000265342.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL4	ENST00000265342.12 linkuse as main transcript	c.1807C>T	p.Leu603Phe	missense_variant	15/16	5	NM_015082.2	P1	Q6MZW2-1
	ENST00000509051.1 linkuse as main transcript	n.76-5884G>A		intron_variant, non_coding_transcript_variant		4
FSTL4	ENST00000509525.5 linkuse as main transcript	n.1025C>T		non_coding_transcript_exon_variant	7/8	2
FSTL4	ENST00000511375.1 linkuse as main transcript	n.487C>T		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000388

AC:

AN:

247652

Hom.:

AF XY:

0.000322

AC XY:

AN XY:

133634

show subpopulations

Gnomad AFR exome

AF:

0.00450

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000166

AC:

241

AN:

1453288

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

107

AN XY:

722924

show subpopulations

Gnomad4 AFR exome

AF:

0.00441

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000515

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152326

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00462

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000488

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000502

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.2

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.24

Sift

Benign

0.10

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.66

MVP

0.42

MPC

0.88

ClinPred

0.047

GERP RS

5.3

Varity_R

0.30

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over