Genetic Variant FSTL1:c.*1162G>A (chr3-120395790-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007085.5(FSTL1):c.*1162G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 501,774 control chromosomes in the GnomAD database, including 2,668 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 0.10 ( 826 hom., cov: 31)

Exomes 𝑓: 0.098 ( 1842 hom. )

Consequence

FSTL1
NM_007085.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.642

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:

BTNL12P (HGNC:52935): (butyrophilin like 12, pseudogene)

BTNL12P links:

MIR198 (HGNC:31570): (microRNA 198) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR198 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL1	NM_007085.5 link	c.*1162G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000295633.8	NP_009016.1	Q12841-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL1	ENST00000295633 link	c.*1162G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_007085.5	ENSP00000295633.3		Q12841-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15372

AN:

151866

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.0920

Gnomad EAS

AF:

0.00617

Gnomad SAS

AF:

0.0943

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.0980

AC:

34286

AN:

349790

Hom.:

1842

Cov.:

AF XY:

0.0990

AC XY:

19834

AN XY:

200310

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0646

Gnomad4 ASJ exome

AF:

0.0828

Gnomad4 EAS exome

AF:

0.00251

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0858

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.101

AC:

15382

AN:

151984

Hom.:

826

Cov.:

AF XY:

0.0994

AC XY:

7383

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0877

Gnomad4 ASJ

AF:

0.0920

Gnomad4 EAS

AF:

0.00619

Gnomad4 SAS

AF:

0.0942

Gnomad4 FIN

AF:

0.0867

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.103

Hom.:

357

Bravo

AF:

0.101

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.0

DANN

Benign

0.81

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over