rs2227395

chr4-154563359-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005141.5(FGB):c.114+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,702 control chromosomes in the GnomAD database, including 2,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2343 hom., cov: 32)
• Consequence: FGB NM_005141.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-154563359-G-A is Benign according to our data. Variant chr4-154563359-G-A is described in ClinVar as [Benign]. Clinvar id is 1285883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGB	NM_005141.5	c.114+227G>A		intron_variant		ENST00000302068.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGB	ENST00000302068.9	c.114+227G>A		intron_variant		1	NM_005141.5	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25512 AN: 151588 Hom.: 2344 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25518 AN: 151702 Hom.: 2343 Cov.: 32 AF XY: 0.165 AC XY: 12259 AN XY: 74146

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.181

Alfa AF: 0.195 Hom.: 493

Bravo AF: 0.167

Asia WGS AF: 0.162 AC: 558 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
Dann	Benign	0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs2227395; hg19: chr4-155484511;