1-27372958-A-T

Position:

• chr1-27372958-A-T

Variant summary

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

The ENST00000270879.9(FCN3):​c.393+178T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,848 control chromosomes in the GnomAD database, including 37,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.69 (37474 hom., cov: 29)
• Consequence: FCN3 ENST00000270879.9 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.153

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN3	NM_003665.4	c.393+178T>A		intron_variant		ENST00000270879.9	NP_003656.2
FCN3	NM_173452.3	c.360+178T>A		intron_variant			NP_775628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN3	ENST00000270879.9	c.393+178T>A		intron_variant		1	NM_003665.4	ENSP00000270879	P2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105391 AN: 151730 Hom.: 37450 Cov.: 29

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.694 AC: 105458 AN: 151848 Hom.: 37474 Cov.: 29 AF XY: 0.701 AC XY: 52034 AN XY: 74228

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.684

Alfa AF: 0.712 Hom.: 4593

Bravo AF: 0.685

Asia WGS AF: 0.836 AC: 2906 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Rheumatic heart disease Uncertain:1

Uncertain significance, 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	-0.86
CADD	Benign	3.6
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10794501; hg19: chr1-27699449;