Variant 8-17864704-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004467.4(FGL1):c.827C>T(p.Thr276Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,612,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

FGL1
NM_004467.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.874

Variant links:

Genes affected

FGL1 (HGNC:3695): (fibrinogen like 1) Fibrinogen-like 1 is a member of the fibrinogen family. This protein is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of fibrinogens and fibrinogen related proteins. However, this protein lacks the platelet-binding site, cross-linking region and a thrombin-sensitive site which are necessary for fibrin clot formation. This protein may play a role in the development of hepatocellular carcinomas. Four alternatively spliced transcript variants encoding the same protein exist for this gene. [provided by RefSeq, Jul 2008]

FGL1 links:

FGL1 (HGNC:):

FGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058511257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL1	NM_004467.4 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	8/8	ENST00000427924.5	NP_004458.3	Q08830

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGL1	ENST00000427924.5 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	8/8	1	NM_004467.4	ENSP00000401952.1		Q08830

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000757

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

247532

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

134082

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000443

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.0000989

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000170

AC:

249

AN:

1460642

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000655

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00313

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000559

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000780

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000757

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.827C>T (p.T276M) alteration is located in exon 9 (coding exon 7) of the FGL1 gene. This alteration results from a C to T substitution at nucleotide position 827, causing the threonine (T) at amino acid position 276 to be replaced by a methionine (M). 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

0.098

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;T;T;T;T;T;T

Eigen

Benign

-0.024

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.86

.;.;.;.;.;D;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.059

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;M;M;M;M;M;M

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0080

D;D;D;D;D;D;D

Sift4G

Uncertain

0.056

T;T;T;T;T;T;T

Polyphen

0.96

P;P;P;P;P;P;P

Vest4

0.37

MVP

0.24

ClinPred

0.058

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.14

gMVP

0.41

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