1-27370983-G-C

Variant names:

• chr1-27370983-G-C
• rs3813800
• NM_003665.4:c.394-11C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency due to ficolin3 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN3	NM_003665.4	MANE Select	c.394-11C>G		intron	N/A	NP_003656.2
	FCN3	NM_173452.3		c.361-11C>G		intron	N/A	NP_775628.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN3	ENST00000270879.9	TSL:1 MANE Select	c.394-11C>G		intron	N/A	ENSP00000270879.4
	FCN3	ENST00000354982.2	TSL:1	c.361-11C>G		intron	N/A	ENSP00000347077.2
	FCN3	ENST00000699963.1		c.394-11C>G		intron	N/A	ENSP00000514719.1

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

GnomAD2 exomes AF: 0.0446 AC: 10987 AN: 246176 AF XY: 0.0509

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 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

African (AFR) AF: 0.0891 AC: 2975 AN: 33402

American (AMR) AF: 0.00571 AC: 255 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00284 AC: 74 AN: 26084

East Asian (EAS) AF: 0.127 AC: 5051 AN: 39652

South Asian (SAS) AF: 0.207 AC: 17856 AN: 86060

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 53030

Middle Eastern (MID) AF: 0.0113 AC: 51 AN: 4512

European-Non Finnish (NFE) AF: 0.000586 AC: 651 AN: 1111174

Other (OTH) AF: 0.0298 AC: 1792 AN: 60172

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

African (AFR) AF: 0.0827 AC: 3434 AN: 41546

American (AMR) AF: 0.00961 AC: 147 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.154 AC: 797 AN: 5166

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4814

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68016

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3813800; hg19: chr1-27697474; COSMIC: COSV54642147; COSMIC: COSV54642147;