rs414884

Variant names:

• chr8-17890609-C-T
• rs414884
• NM_004467.4:c.-18+4838G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004467.4(FGL1):​c.-18+4838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,952 control chromosomes in the GnomAD database, including 34,429 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 0.67 (34429 hom., cov: 31)
• Consequence: FGL1 NM_004467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGL1	NM_004467.4	c.-18+4838G>A		intron_variant	Intron 1 of 7	ENST00000427924.5	NP_004458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGL1	ENST00000427924.5	c.-18+4838G>A		intron_variant	Intron 1 of 7	1	NM_004467.4	ENSP00000401952.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101140 AN: 151832 Hom.: 34414 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.666 AC: 101187 AN: 151952 Hom.: 34429 Cov.: 31 AF XY: 0.660 AC XY: 49015 AN XY: 74244

African (AFR) AF: 0.626 AC: 25941 AN: 41424

American (AMR) AF: 0.513 AC: 7828 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2404 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2237 AN: 5154

South Asian (SAS) AF: 0.536 AC: 2582 AN: 4818

European-Finnish (FIN) AF: 0.764 AC: 8029 AN: 10516

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49939 AN: 67990

Other (OTH) AF: 0.679 AC: 1435 AN: 2114

Alfa AF: 0.710 Hom.: 19546

Bravo AF: 0.644

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.086
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs414884; hg19: chr8-17748118;