rs6056

Positions:

chr4-154567669-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.567C>T(p.Ser189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,611,650 control chromosomes in the GnomAD database, including 24,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2019 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22535 hom. )

Consequence

FGB
NM_005141.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0580

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:

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=-0.77).

BP6

Variant 4-154567669-C-T is Benign according to our data. Variant chr4-154567669-C-T is described in ClinVar as [Benign]. Clinvar id is 259648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-154567669-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.058 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.567C>T	p.Ser189=	synonymous_variant	4/8	ENST00000302068.9	NP_005132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FGB	ENST00000302068.9 linkuse as main transcript	c.567C>T	p.Ser189=	synonymous_variant	4/8	1	NM_005141.5	ENSP00000306099	P1
FGB	ENST00000509493.1 linkuse as main transcript	c.-91C>T		5_prime_UTR_variant	2/6	5		ENSP00000426757
FGB	ENST00000473984.1 linkuse as main transcript	n.480C>T		non_coding_transcript_exon_variant	3/3	2
FGB	ENST00000502545.5 linkuse as main transcript	n.548C>T		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23549

AN:

151962

Hom.:

2019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.170

GnomAD3 exomes

AF:

0.172

AC:

43245

AN:

251150

Hom.:

4046

AF XY:

0.175

AC XY:

23783

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.172

AC:

251506

AN:

1459570

Hom.:

22535

Cov.:

AF XY:

0.173

AC XY:

125966

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.0880

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.155

AC:

23566

AN:

152080

Hom.:

2019

Cov.:

AF XY:

0.152

AC XY:

11333

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.185

Hom.:

6641

Bravo

AF:

0.154

Asia WGS

AF:

0.162

AC:

563

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	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

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

-0.77

CADD

Benign

3.8

DANN

Benign

0.55

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