Variant chr3-120402809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007085.5(FSTL1):c.804C>T(p.Asp268=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 1,556,806 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 11 hom., cov: 31)

Exomes 𝑓: 0.0091 ( 110 hom. )

Consequence

FSTL1
NM_007085.5 splice_region, synonymous

Scores

Splicing: ADA: 0.0003314

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.99

Variant links:

Genes affected

FSTL1 (HGNC:3972): (follistatin like 1) This gene encodes a protein with similarity to follistatin, an activin-binding protein. It contains an FS module, a follistatin-like sequence containing 10 conserved cysteine residues. This gene product is thought to be an autoantigen associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

FSTL1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 3-120402809-G-A is Benign according to our data. Variant chr3-120402809-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 784017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.99 with no splicing effect.

BS2

High AC in GnomAd4 at 1112 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL1	NM_007085.5 linkuse as main transcript	c.804C>T	p.Asp268=	splice_region_variant, synonymous_variant	9/11	ENST00000295633.8
LRRC58-DT	XR_007096031.1 linkuse as main transcript	n.964-12992G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL1	ENST00000295633.8 linkuse as main transcript	c.804C>T	p.Asp268=	splice_region_variant, synonymous_variant	9/11	1	NM_007085.5	P1	Q12841-1
	ENST00000494869.2 linkuse as main transcript	n.633-12992G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1111

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00177

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00904

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00821

AC:

2062

AN:

251070

Hom.:

AF XY:

0.00800

AC XY:

1085

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00911

AC:

12804

AN:

1404834

Hom.:

110

Cov.:

AF XY:

0.00877

AC XY:

6161

AN XY:

702440

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000517

Gnomad4 FIN exome

AF:

0.0356

Gnomad4 NFE exome

AF:

0.00973

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.00732

AC:

1112

AN:

151972

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

584

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00367

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00765

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	FSTL1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.33

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00033

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.070

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