chr4-154569680-C-T

Position:

chr4-154569680-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005141.5(FGB):c.1125C>T(p.Tyr375Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,736 control chromosomes in the GnomAD database, including 24,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1881 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22285 hom. )

Consequence

FGB
NM_005141.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.270

Variant links:

Genes affected

FGB (HGNC:3662): (fibrinogen beta chain) The protein encoded by this gene is the beta component of fibrinogen, a blood-borne glycoprotein comprised of three pairs of nonidentical polypeptide chains. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots. In addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Fibrinogen serves key roles in hemostasis and antimicrobial host defense. Mutations in this gene lead to several disorders, including afibrinogenemia, dysfibrinogenemia, hypodysfibrinogenemia and thrombotic tendency. [provided by RefSeq, Aug 2020]

FGB links:

FGB (HGNC:):

FGB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 4-154569680-C-T is Benign according to our data. Variant chr4-154569680-C-T is described in ClinVar as [Benign]. Clinvar id is 259645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-154569680-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGB	NM_005141.5 linkuse as main transcript	c.1125C>T	p.Tyr375Tyr	synonymous_variant	7/8	ENST00000302068.9	NP_005132.2	P02675V9HVY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FGB	ENST00000302068.9 linkuse as main transcript	c.1125C>T	p.Tyr375Tyr	synonymous_variant	7/8	1	NM_005141.5	ENSP00000306099.4	P02675
FGB	ENST00000509493.1 linkuse as main transcript	c.468C>T	p.Tyr156Tyr	synonymous_variant	5/6	5		ENSP00000426757.1	D6REL8
FGB	ENST00000502545.5 linkuse as main transcript	n.939+373C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21571

AN:

151956

Hom.:

1882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.168

AC:

42183

AN:

251194

Hom.:

3940

AF XY:

0.172

AC XY:

23303

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.171

AC:

249744

AN:

1461662

Hom.:

22285

Cov.:

AF XY:

0.172

AC XY:

125096

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0435

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.142

AC:

21575

AN:

152074

Hom.:

1881

Cov.:

AF XY:

0.140

AC XY:

10434

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0473

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.178

Hom.:

3462

Bravo

AF:

0.139

Asia WGS

AF:

0.156

AC:

543

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.184

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital afibrinogenemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.23

DANN

Benign

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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