rs7037264

Positions:

• chr9-134883366-G-A
• chr9-134883366-G-C

Variant summary

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

The NM_004108.3(FCN2):​c.268+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,610,220 control chromosomes in the GnomAD database, including 142,686 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 0.47 (17874 hom., cov: 30)
  • Exomes 𝑓: 0.41 (124812 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.268+11G>A		intron_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.154+11G>A		intron_variant			NP_056652.1
FCN2	XM_011518392.4	c.235+11G>A		intron_variant			XP_011516694.1
FCN2	XM_006717015.5	c.121+11G>A		intron_variant			XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.268+11G>A		intron_variant		1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.154+11G>A		intron_variant		5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72040 AN: 151770 Hom.: 17830 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.431 AC: 107838 AN: 250132 Hom.: 24016 AF XY: 0.422 AC XY: 57181 AN XY: 135422

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.531

Gnomad SAS exome AF: 0.397

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.410 AC: 598023 AN: 1458334 Hom.: 124812 Cov.: 33 AF XY: 0.409 AC XY: 296828 AN XY: 725688

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.475 AC: 72139 AN: 151886 Hom.: 17874 Cov.: 30 AF XY: 0.475 AC XY: 35223 AN XY: 74212

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.431

Alfa AF: 0.426 Hom.: 10191

Bravo AF: 0.484

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.73

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: rs7037264; hg19: chr9-137775212; COSMIC: COSV52475894;