chr4-154565318-T-A

Position:

• chr4-154565318-T-A

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.115-490T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 304,438 control chromosomes in the GnomAD database, including 4,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2356 hom., cov: 32)
  • Exomes 𝑓: 0.15 (2048 hom.)
• Consequence: FGB NM_005141.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.677

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-154565318-T-A is Benign according to our data. Variant chr4-154565318-T-A is described in ClinVar as [Benign]. Clinvar id is 1256963.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	UniProt
FGB	NM_005141.5	c.115-490T>A		intron_variant		ENST00000302068.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGB	ENST00000302068.9	c.115-490T>A		intron_variant		1	NM_005141.5	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25612 AN: 152006 Hom.: 2357 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.154 AC: 23391 AN: 152314 Hom.: 2048 Cov.: 0 AF XY: 0.152 AC XY: 13033 AN XY: 85962

Gnomad4 AFR exome AF: 0.0735

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.168 AC: 25619 AN: 152124 Hom.: 2356 Cov.: 32 AF XY: 0.166 AC XY: 12319 AN XY: 74366

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.149

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: 0.196 Hom.: 462

Bravo AF: 0.167

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.61

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: rs2227402; hg19: chr4-155486470;