Variant chr8-17868592-T-G 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_004467.4(FGL1):c.735A>C(p.Glu245Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,461,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

FGL1
NM_004467.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.411

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:

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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=0.038465887).

BP6

Variant 8-17868592-T-G is Benign according to our data. Variant chr8-17868592-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2538703.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL1	NM_004467.4 linkuse as main transcript	c.735A>C	p.Glu245Asp	missense_variant	7/8	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.735A>C	p.Glu245Asp	missense_variant	7/8	1	NM_004467.4	ENSP00000401952.1		Q08830

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251178

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.14

DANN

Benign

0.43

DEOGEN2

Benign

0.0025

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.46

.;.;.;.;.;T;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.038

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.14

N;N;N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.99

N;N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.57

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

Sift4G

Benign

0.40

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

Polyphen

0.0020

B;B;B;B;B;B;B

Vest4

0.25

MutPred

0.40

Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);Gain of disorder (P = 0.2005);

MVP

0.34

ClinPred

0.012

GERP RS

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.27

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