Variant 4-154565494-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005141.5(FGB):c.115-314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 348,362 control chromosomes in the GnomAD database, including 5,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2354 hom., cov: 32)

Exomes 𝑓: 0.18 ( 3561 hom. )

Consequence

FGB
NM_005141.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.245

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 4-154565494-T-C is Benign according to our data. Variant chr4-154565494-T-C is described in ClinVar as [Benign]. Clinvar id is 1241440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	c.115-314T>C		intron_variant		ENST00000302068.9	NP_005132.2	P02675V9HVY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGB	ENST00000302068.9 link	c.115-314T>C		intron_variant		1	NM_005141.5	ENSP00000306099.4		P02675

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25626

AN:

152080

Hom.:

2355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.183

AC:

35905

AN:

196162

Hom.:

3561

Cov.:

AF XY:

0.182

AC XY:

19025

AN XY:

104552

show subpopulations

Gnomad4 AFR exome

AF:

0.0981

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.168

AC:

25633

AN:

152200

Hom.:

2354

Cov.:

AF XY:

0.166

AC XY:

12331

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0989

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.198

Hom.:

746

Bravo

AF:

0.167

Asia WGS

AF:

0.162

AC:

564

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.1

DANN

Benign

0.39

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