rs1044291

Positions:

• chr4-154572200-C-T

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.*1550C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,010 control chromosomes in the GnomAD database, including 5,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5574 hom., cov: 32)
• Consequence: FGB NM_005141.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271

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=-0.9).
• BP6: Variant 4-154572200-C-T is Benign according to our data. Variant chr4-154572200-C-T is described in ClinVar as [Benign]. Clinvar id is 347799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGB	NM_005141.5	c.*1550C>T		3_prime_UTR_variant	8/8	ENST00000302068.9	NP_005132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGB	ENST00000302068.9	c.*1550C>T		3_prime_UTR_variant	8/8	1	NM_005141.5	ENSP00000306099	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38966 AN: 151892 Hom.: 5575 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.256 AC: 38958 AN: 152010 Hom.: 5574 Cov.: 32 AF XY: 0.252 AC XY: 18700 AN XY: 74272

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.286

Alfa AF: 0.318 Hom.: 8249

Bravo AF: 0.248

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital afibrinogenemia Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1044291; hg19: chr4-155493352;