1-27370983-G-C

Position:

• chr1-27370983-G-C

Variant summary

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

The NM_003665.4(FCN3):​c.394-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,610,992 control chromosomes in the GnomAD database, including 3,102 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 0.037 (369 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2733 hom.)
• Consequence: FCN3 NM_003665.4 intron
• Scores: Splicing: ADA: 0.0005963
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

Genes affected

FCN3 (HGNC:3625): (ficolin 3) Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins, both of which have lectin activity. The protein encoded by this gene is a thermolabile beta-2-macroglycoprotein found in all human serum and is a member of the ficolin/opsonin p35 lectin family. The protein, which was initially identified based on its reactivity with sera from patients with systemic lupus erythematosus, has been shown to have a calcium-independent lectin activity. The protein can activate the complement pathway in association with MASPs and sMAP, thereby aiding in host defense through the activation of the lectin pathway. Alternative splicing occurs at this locus and two variants, each encoding a distinct isoform, have been identified. [provided by RefSeq, Jul 2008]

FCN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN3	NM_003665.4	c.394-11C>G		intron_variant		ENST00000270879.9	NP_003656.2
FCN3	NM_173452.3	c.361-11C>G		intron_variant			NP_775628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN3	ENST00000270879.9	c.394-11C>G		intron_variant		1	NM_003665.4	ENSP00000270879.4

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5604 AN: 152128 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0446 AC: 10987 AN: 246176 Hom.: 1059 AF XY: 0.0509 AC XY: 6824 AN XY: 133984

Gnomad AFR exome AF: 0.0859

Gnomad AMR exome AF: 0.00517

Gnomad ASJ exome AF: 0.00253

Gnomad EAS exome AF: 0.155

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000979

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0197 AC: 28711 AN: 1458746 Hom.: 2733 Cov.: 32 AF XY: 0.0250 AC XY: 18170 AN XY: 725472

Gnomad4 AFR exome AF: 0.0891

Gnomad4 AMR exome AF: 0.00571

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.000586

Gnomad4 OTH exome AF: 0.0298

GnomAD4 genome AF: 0.0368 AC: 5606 AN: 152246 Hom.: 369 Cov.: 32 AF XY: 0.0412 AC XY: 3065 AN XY: 74430

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.00961

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00413 Hom.: 7

Bravo AF: 0.0337

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00060
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.050		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: rs3813800; hg19: chr1-27697474; COSMIC: COSV54642147; COSMIC: COSV54642147;