NM_005141.5:c.*1550C>T

Variant names:

• chr4-154572200-C-T
• rs1044291
• NM_005141.5:c.*1550C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• congenital fibrinogen deficiency

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• thrombophilia

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
• congenital afibrinogenemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• familial dysfibrinogenemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial hypofibrinogenemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005141.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGB	NM_005141.5	MANE Select	c.*1550C>T		3_prime_UTR	Exon 8 of 8	NP_005132.2
	FGB	NM_001382763.1		c.*1550C>T		3_prime_UTR	Exon 8 of 8	NP_001369692.1
	FGB	NM_001382765.1		c.*1550C>T		3_prime_UTR	Exon 8 of 8	NP_001369694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGB	ENST00000302068.9	TSL:1 MANE Select	c.*1550C>T		3_prime_UTR	Exon 8 of 8	ENSP00000306099.4

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

African (AFR) AF: 0.147 AC: 6097 AN: 41454

American (AMR) AF: 0.224 AC: 3426 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3470

East Asian (EAS) AF: 0.140 AC: 723 AN: 5170

South Asian (SAS) AF: 0.310 AC: 1490 AN: 4810

European-Finnish (FIN) AF: 0.244 AC: 2576 AN: 10556

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22661 AN: 67970

Other (OTH) AF: 0.286 AC: 602 AN: 2108

Alfa AF: 0.307 Hom.: 20152

Bravo AF: 0.248

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital afibrinogenemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.20
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs1044291; hg19: chr4-155493352;