rs12684512

Positions:

• chr9-134885658-G-A

Variant summary

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

The ENST00000291744.11(FCN2):​c.430-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,470,876 control chromosomes in the GnomAD database, including 10,460 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 0.13 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9094 hom.)
• Consequence: FCN2 ENST00000291744.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.430-110G>A		intron_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.316-110G>A		intron_variant			NP_056652.1
FCN2	XM_006717015.5	c.283-110G>A		intron_variant			XP_006717078.1
FCN2	XM_011518392.4	c.397-110G>A		intron_variant			XP_011516694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.430-110G>A		intron_variant		1	NM_004108.3	ENSP00000291744	P1
FCN2	ENST00000350339.3	c.316-110G>A		intron_variant		5		ENSP00000291741

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19795 AN: 151860 Hom.: 1365 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.114 AC: 150420 AN: 1318898 Hom.: 9094 AF XY: 0.114 AC XY: 74828 AN XY: 658886

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.0463

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.130 AC: 19820 AN: 151978 Hom.: 1366 Cov.: 32 AF XY: 0.129 AC XY: 9600 AN XY: 74304

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.129

Alfa AF: 0.114 Hom.: 826

Bravo AF: 0.135

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.72

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: rs12684512; hg19: chr9-137777504;