1-27370346-G-T

Position:

• chr1-27370346-G-T

Variant summary

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

The NM_003665.4(FCN3):​c.658+250C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 484,418 control chromosomes in the GnomAD database, including 19,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5311 hom., cov: 32)
  • Exomes 𝑓: 0.28 (14093 hom.)
• Consequence: FCN3 NM_003665.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.403

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN3	NM_003665.4	c.658+250C>A		intron_variant		ENST00000270879.9
FCN3	NM_173452.3	c.625+250C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN3	ENST00000270879.9	c.658+250C>A		intron_variant		1	NM_003665.4	P2
FCN3	ENST00000354982.2	c.625+250C>A		intron_variant		1		A2
FCN3	ENST00000699963.1	c.*242C>A		3_prime_UTR_variant	7/7
FCN3	ENST00000699962.1	n.657+250C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37467 AN: 151972 Hom.: 5310 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.277 AC: 91900 AN: 332328 Hom.: 14093 AF XY: 0.272 AC XY: 47662 AN XY: 175072

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.246 AC: 37472 AN: 152090 Hom.: 5311 Cov.: 32 AF XY: 0.242 AC XY: 18022 AN XY: 74344

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.279

Alfa AF: 0.284 Hom.: 1089

Bravo AF: 0.244

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Rheumatic heart disease Other:1

risk factor, no assertion criteria provided

case-control

Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University

Jan 09, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.66

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: rs4494157; hg19: chr1-27696837;