rs2227401

Positions:

• chr4-154565229-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005141.5(FGB):​c.115-579C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 461,956 control chromosomes in the GnomAD database, including 8,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2350 hom., cov: 32)
  • Exomes 𝑓: 0.18 (5746 hom.)
• Consequence: FGB NM_005141.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-154565229-C-T is Benign according to our data. Variant chr4-154565229-C-T is described in ClinVar as [Benign]. Clinvar id is 1234634.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	c.115-579C>T		intron_variant		ENST00000302068.9	NP_005132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGB	ENST00000302068.9	c.115-579C>T		intron_variant		1	NM_005141.5	ENSP00000306099.4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25591 AN: 152044 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.218

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

GnomAD3 exomes AF: 0.175 AC: 24303 AN: 139070 Hom.: 2341 AF XY: 0.178 AC XY: 13382 AN XY: 75226

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.184 AC: 57132 AN: 309792 Hom.: 5746 Cov.: 0 AF XY: 0.186 AC XY: 32596 AN XY: 175528

Gnomad4 AFR exome AF: 0.0928

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.168 AC: 25598 AN: 152164 Hom.: 2350 Cov.: 32 AF XY: 0.165 AC XY: 12314 AN XY: 74410

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.148

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: 0.203 Hom.: 3093

Bravo AF: 0.167

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.91
CADD	Benign	2.6
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2227401; hg19: chr4-155486381;