rs140114081

chr4-154569497-TTTTG-Tchr4-154569497-TTTTG-TTTTGTTTG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005141.5(FGB):c.959-13_959-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,606,216 control chromosomes in the GnomAD database, including 23,864 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1851 hom., cov: 29)
  • Exomes 𝑓: 0.17 (22013 hom.)
• Consequence: FGB NM_005141.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.53

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 -16 ACMG points.

• BP6: Variant 4-154569497-TTTTG-T is Benign according to our data. Variant chr4-154569497-TTTTG-T is described in ClinVar as [Benign]. Clinvar id is 259650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-154569497-TTTTG-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGB	NM_005141.5	c.959-13_959-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000302068.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGB	ENST00000302068.9	c.959-13_959-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005141.5	P1
FGB	ENST00000509493.1	c.302-13_302-10del		splice_polypyrimidine_tract_variant, intron_variant		5
FGB	ENST00000502545.5	n.939+194_939+197del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21525 AN: 152020 Hom.: 1852 Cov.: 29

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.164 AC: 39685 AN: 241336 Hom.: 3598 AF XY: 0.168 AC XY: 21990 AN XY: 131052

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.170 AC: 247039 AN: 1454078 Hom.: 22013 AF XY: 0.171 AC XY: 123651 AN XY: 723020

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.142 AC: 21529 AN: 152138 Hom.: 1851 Cov.: 29 AF XY: 0.140 AC XY: 10388 AN XY: 74350

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.155

Alfa AF: 0.179 Hom.: 514

Bravo AF: 0.139

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital afibrinogenemia Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140114081; hg19: chr4-155490649;