8-17878362-C-T

Position:

• chr8-17878362-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004467.4(FGL1):​c.244+3637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,006 control chromosomes in the GnomAD database, including 22,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22876 hom., cov: 32)
• Consequence: FGL1 NM_004467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

FGL1 (HGNC:3695): (fibrinogen like 1) Fibrinogen-like 1 is a member of the fibrinogen family. This protein is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of fibrinogens and fibrinogen related proteins. However, this protein lacks the platelet-binding site, cross-linking region and a thrombin-sensitive site which are necessary for fibrin clot formation. This protein may play a role in the development of hepatocellular carcinomas. Four alternatively spliced transcript variants encoding the same protein exist for this gene. [provided by RefSeq, Jul 2008]

FGL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL1	NM_004467.4	c.244+3637G>A		intron_variant		ENST00000427924.5	NP_004458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGL1	ENST00000427924.5	c.244+3637G>A		intron_variant		1	NM_004467.4	ENSP00000401952.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77953 AN: 151888 Hom.: 22877 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.513 AC: 77957 AN: 152006 Hom.: 22876 Cov.: 32 AF XY: 0.508 AC XY: 37752 AN XY: 74312

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.547

Alfa AF: 0.542 Hom.: 5164

Bravo AF: 0.486

Asia WGS AF: 0.431 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9325823; hg19: chr8-17735871;