rs1800787

Variant names:

• chr4-154562863-C-T
• rs1800787
• NM_005141.5:c.-156C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154562863-C-T
• chr4-154562863-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005141.5(FGB):​c.-156C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 542,310 control chromosomes in the GnomAD database, including 9,817 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: 0.19 (7467 hom.)
• Consequence: FGB NM_005141.5 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0140
• Publications: 35 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 4-154562863-C-T is Benign according to our data. Variant chr4-154562863-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 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.-156C>T		upstream_gene	N/A	NP_005132.2	P02675
	FGB	NM_001382763.1		c.-156C>T		upstream_gene	N/A	NP_001369692.1
	FGB	NM_001382765.1		c.-156C>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.-156C>T		upstream_gene	N/A	ENSP00000306099.4	P02675
	FGB	ENST00000497097.5	TSL:1	n.-149C>T		upstream_gene	N/A
	FGB	ENST00000904942.1		c.-156C>T		upstream_gene	N/A	ENSP00000575001.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25559 AN: 151806 Hom.: 2351 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: 0.237

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.190 AC: 74003 AN: 390386 Hom.: 7467 AF XY: 0.190 AC XY: 39757 AN XY: 209042

African (AFR) AF: 0.102 AC: 1120 AN: 11000

American (AMR) AF: 0.147 AC: 2096 AN: 14282

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 2546 AN: 12406

East Asian (EAS) AF: 0.162 AC: 4438 AN: 27446

South Asian (SAS) AF: 0.153 AC: 5395 AN: 35338

European-Finnish (FIN) AF: 0.176 AC: 5098 AN: 29042

Middle Eastern (MID) AF: 0.241 AC: 417 AN: 1732

European-Non Finnish (NFE) AF: 0.206 AC: 48649 AN: 236614

Other (OTH) AF: 0.188 AC: 4244 AN: 22526

GnomAD4 genome AF: 0.168 AC: 25566 AN: 151924 Hom.: 2350 Cov.: 32 AF XY: 0.165 AC XY: 12287 AN XY: 74254

African (AFR) AF: 0.0987 AC: 4097 AN: 41494

American (AMR) AF: 0.148 AC: 2265 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3462

East Asian (EAS) AF: 0.217 AC: 1125 AN: 5180

South Asian (SAS) AF: 0.156 AC: 752 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1863 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14092 AN: 67814

Other (OTH) AF: 0.182 AC: 385 AN: 2112

Alfa AF: 0.195 Hom.: 3704

Bravo AF: 0.167

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FIBRINOGEN, BETA-148 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.40
PhyloP100		0.014
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1800787; hg19: chr4-155484015;