rs1800788

Variant names:

• chr4-154562762-C-T
• rs1800788
• NM_005141.5:c.-257C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154562762-C-T
• chr4-154562762-C-G

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.-257C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,786 control chromosomes in the GnomAD database, including 3,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3307 hom., cov: 32)
• Consequence: FGB NM_005141.5 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 38 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=-0.86).
• BP6: Variant 4-154562762-C-T is Benign according to our data. Variant chr4-154562762-C-T is described in ClinVar as Benign. ClinVar VariationId is 1290152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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.-257C>T		upstream_gene	N/A	NP_005132.2	P02675
	FGB	NM_001382763.1		c.-257C>T		upstream_gene	N/A	NP_001369692.1
	FGB	NM_001382765.1		c.-257C>T		upstream_gene	N/A	NP_001369694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGB	ENST00000302068.9	TSL:1 MANE Select	c.-257C>T		upstream_gene	N/A	ENSP00000306099.4	P02675
	FGB	ENST00000497097.5	TSL:1	n.-250C>T		upstream_gene	N/A
	FGB	ENST00000904942.1		c.-257C>T		upstream_gene	N/A	ENSP00000575001.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28338 AN: 151668 Hom.: 3309 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.187 AC: 28341 AN: 151786 Hom.: 3307 Cov.: 32 AF XY: 0.193 AC XY: 14307 AN XY: 74174

African (AFR) AF: 0.0874 AC: 3624 AN: 41480

American (AMR) AF: 0.211 AC: 3222 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2830 AN: 5164

South Asian (SAS) AF: 0.244 AC: 1172 AN: 4804

European-Finnish (FIN) AF: 0.258 AC: 2716 AN: 10536

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13591 AN: 67782

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.202 Hom.: 8615

Bravo AF: 0.181

Asia WGS AF: 0.346 AC: 1197 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.020
DANN	Benign	0.49
PhyloP100		-1.3
PromoterAI		0.0059	Neutral
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1800788; hg19: chr4-155483914;