rs12685659

Positions:

• chr9-134884873-A-T

Variant summary

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

The ENST00000291744.11(FCN2):​c.301+101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,068,764 control chromosomes in the GnomAD database, including 6,197 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 0.083 (652 hom., cov: 33)
  • Exomes 𝑓: 0.10 (5545 hom.)
• Consequence: FCN2 ENST00000291744.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.301+101A>T		intron_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.187+101A>T		intron_variant			NP_056652.1
FCN2	XM_006717015.5	c.154+101A>T		intron_variant			XP_006717078.1
FCN2	XM_011518392.4	c.268+101A>T		intron_variant			XP_011516694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.301+101A>T		intron_variant		1	NM_004108.3	ENSP00000291744	P1
FCN2	ENST00000350339.3	c.187+101A>T		intron_variant		5		ENSP00000291741

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12658 AN: 152190 Hom.: 652 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0860

GnomAD4 exome AF: 0.105 AC: 96045 AN: 916456 Hom.: 5545 AF XY: 0.105 AC XY: 49636 AN XY: 472482

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0396

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.0832 AC: 12668 AN: 152308 Hom.: 652 Cov.: 33 AF XY: 0.0838 AC XY: 6242 AN XY: 74478

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0991 Hom.: 97

Bravo AF: 0.0812

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs12685659; hg19: chr9-137776719; COSMIC: COSV52477163;