Genetic Variant FBRS:p.Thr675Ala (chr16-30667571-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001105079.3(FBRS):c.2023A>G(p.Thr675Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,542,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

FBRS
NM_001105079.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

FBRS (HGNC:20442): (fibrosin) Fibrosin is a lymphokine secreted by activated lymphocytes that induces fibroblast proliferation (Prakash and Robbins, 1998 [PubMed 9809749]).[supplied by OMIM, Mar 2008]

FBRS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009007424).

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRS	NM_001105079.3 link	c.2023A>G	p.Thr675Ala	missense_variant	Exon 15 of 18	ENST00000356166.11	NP_001098549.2	Q9HAH7J3KNZ9B3KTZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRS	ENST00000356166.11 link	c.2023A>G	p.Thr675Ala	missense_variant	Exon 15 of 18	5	NM_001105079.3	ENSP00000348489.5		J3KNZ9

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000309

AC:

AN:

148758

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

78338

show subpopulations

Gnomad AFR exome

AF:

0.000116

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00266

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.000707

GnomAD4 exome

AF:

0.000123

AC:

171

AN:

1390866

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

685906

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.00277

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000502

Gnomad4 OTH exome

AF:

0.000382

GnomAD4 genome

AF:

0.000263

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000250

AC:

ExAC

AF:

0.000109

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463A>G (p.T155A) alteration is located in exon 9 (coding exon 8) of the FBRS gene. This alteration results from a A to G substitution at nucleotide position 463, causing the threonine (T) at amino acid position 155 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.065

Sift

Benign

0.53

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.018

.;B

Vest4

0.45

MVP

0.043

MPC

0.36

ClinPred

0.0090

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.22

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