1-27370346-G-A

Variant names:

• chr1-27370346-G-A
• rs4494157
• NM_003665.4:c.658+250C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003665.4(FCN3):​c.658+250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCN3 NM_003665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN3	NM_003665.4	c.658+250C>T		intron_variant	Intron 7 of 7	ENST00000270879.9	NP_003656.2
FCN3	NM_173452.3	c.625+250C>T		intron_variant	Intron 6 of 6		NP_775628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN3	ENST00000270879.9	c.658+250C>T		intron_variant	Intron 7 of 7	1	NM_003665.4	ENSP00000270879.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 333296 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 175542

African (AFR) AF: 0.00 AC: 0 AN: 10176

American (AMR) AF: 0.00 AC: 0 AN: 11750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10472

East Asian (EAS) AF: 0.00 AC: 0 AN: 23160

South Asian (SAS) AF: 0.00 AC: 0 AN: 33898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1474

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 202018

Other (OTH) AF: 0.00 AC: 0 AN: 19390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		-0.40

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: rs4494157; hg19: chr1-27696837;